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D M Nance

Publications and source records attributed to D M Nance.

At least 19 recordsLinked to original sources

Quantitative immunohistochemical and biochemical correlates of connexin43 localization in rat brain.

We have shown by immunohistochemical methods that the gap junction protein connexin43 is heterogeneously distributed in rat brain (Yamamoto et al: J Comp Neurol 302:853, 1990). Here we have compared quantitatively the relative amount of connexin43 detected on Western blots of seven central nervous system (CNS) regions with the density of connexin43-immunoperoxidase reactivity in these regions. As has been observed on Western blots of several cell types, homogenates of these CNS regions contained two forms of connexin43, its dephospho form with an apparent mobility of approximately 41 kDa and its approximately 43 kDa phosphorylated form. While the relative quantities of connexin43 varied considerably among the brain regions, the ratio of the 43/41 kDa forms, 0.71, was relatively uniform (correlation coefficient, r = 0.92). Sections of brain processed for connexin43-immunolocalization by the peroxidase-antiperoxidase (PAP) method showed that chromogen deposition was linear with incubation time in reaction medium. Optical density of tissue connexin43-immunoreactivity in each of the seven areas plotted against the density of connexin43 bands on Western blots gave a correlation coefficient of r = 0.90. Connexin43-immunoreactivity had a similar appearance in sections processed by PAP or immunofluorescence procedures and consisted of isolated or aggregates of puncta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility.

A cDNA encoding a unique hyaluronan receptor has been molecularly cloned from a lambda GT11 3T3 cDNA expression library. Immunoblot analyses of cell lysates, using antibodies to peptides encoded in the cDNA, specifically react with a 58-kD protein. This protein is regulated by the mutant H-ras gene in cells containing a metallothionein promoter H-ras hybrid gene. Further, antibodies to peptide sequences encoded in the cDNA block the increase in locomotion resulting from induction of the mutant H-ras gene in this cell line. In a transblot assay, the bacterially expressed protein binds to biotinylated hyaluronan. Antibodies to peptides encoded in the cDNA react in immunoblot assays with the 58- and 52-kD proteins of a novel hyaluronan receptor complex previously implicated in cell locomotion. Furthermore, antibodies specific to the 58- and 52-kD proteins, which block ras-induced locomotion, also cross-react with the expressed, encoded protein. The gene product described here appears to be a new type of hyaluronan receptor that is involved in cell locomotion. It is named RHAMM, an acronym for receptor for hyaluronan-mediated motility.

3T3 Cells

Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1 beta: evidence for pituitary-adrenal and sympathetic control.

Intracerebroventricular (ICV) injections of interleukin-1 beta (IL-1 beta) produced a dose-dependent increase in plasma corticosterone and adrenocorticotropic hormone (ACTH) within 2 hr of injection and then declined over the next 24 hr. Using a potent steroidogenic dose of IL-1 beta (5 ng), ICV injection resulted in suppression of splenic macrophage IL-1 secretion following stimulation by LPS in vitro. Macrophage TGF-beta secretion was not affected, indicating a differential action of ICV IL-1 beta on macrophage cytokine production. Following adrenalectomy (ADX), the suppressive effect of ICV IL-1 beta was reversed and resulted in stimulation of macrophage IL-1 secretion, indicating that the suppression was mediated by adrenocorticol activation. However, surgical interruption of the splenic nerve to eliminate autonomic innervation of the spleen also prevented the macrophage suppressive signal in rats given ICV IL-1 beta. Furthermore, the combination of ADX and splenic nerve section resulted in a potent stimulatory effect of ICV IL-1 beta on splenic macrophage IL-1 secretion which was greater than either ADX or splenic nerve section alone. These results support the concept of a negative feedback on macrophage IL-1 secretion by the central action of IL-1 beta and indicate that both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system mediate this effect.

Adrenalectomy

Differential and sex-specific effects of kainic acid and domoic acid lesions in the lateral septal area of rats on immune function and body weight regulation.

The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats.

Animals

Fluorescent dextrans as sensitive anterograde neuroanatomical tracers: applications and pitfalls.

We have examined five conjugated 10,000 mol. wt. dextrans as potential anterograde tract tracers: Lucifer Yellow, Texas Red, fluorescein, Cascade Blue and tetramethylrhodamine. Pressure injections were made into the brain, dorsal root ganglia or footpads of adult rats. The retrograde tracer Fluoro-Gold was injected alone or mixed with the dextrans before injection. Three-14 days after injection, animals were perfused and sections cut with a freezing microtome. Texas Red-, fluorescein- and tetramethylrhodamine-conjugated dextrans produced intense labeling of neuronal cell bodies, axons and dendritic processes at the injection site and were transported by neurons predominantly in an anterograde direction to yield terminal and preterminal labeling. Relative to the fluorescein and tetramethylrhodamine conjugates, the quality and intensity of the anterograde labeling produced by Texas Red was variable. Results with Lucifer Yellow and Cascade Blue conjugates were negative. Optimal results were produced by slow-pressure injections via glass micropipettes. In comparison with Fluoro-Gold, retrograde transport by the dextran conjugates was present, but limited in its extent. Injections of the tetramethylrhodamine conjugate into dorsal root ganglia produced anterograde labeling of afferent fibers in visceral organs and injections into the nucleus ambiguous labeled motor fibers in the esophagus. Double/triple labeling was observed in the brain and spinal cord following multiple injections of fluorescein, tetramethylrhodamine and Fluoro-Gold. Also, Fluoro-Gold could be mixed with one of the dextrans in order to produce specific retrograde and anterograde labeling from the same injection site. The conjugates were compatible with fluorescent immunocytochemical procedures, but proved unsuitable for peripheral injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Innervation of the spleen in the rat: evidence for absence of afferent innervation.

Catecholaminergic fibers in the spleen have been well characterized in the rat and this innervation is believed to be an important source of modulation of the immune system. The presence or role of afferent feedback from the spleen has not been systematically investigated. We have examined whether the spleen receives afferent innervation from sensory ganglia and also have assessed the sources of efferent innervation to the spleen in the rat. The fluorescent retrograde anatomical tracers fluoro-gold (FGo) or fast blue (FB) were injected into the spleens of adult female rats and dorsal root, sympathetic chain, nodose, and celiac-mesenteric plexus ganglia were collected. In additional animals, the spleen was either injected with the anatomical tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) or else regular HRP was applied to the cut end of the splenic nerve. Also, we examined the effects of cutting the splenic nerve on the retrograde labeling of cell bodies in the ganglia and on the catecholamine histochemistry of the spleen. The neuroanatomical results were based primarily upon the tracer FGo and verified that the celiac-mesenteric plexus ganglia provide a major efferent input to the spleen. Furthermore, lower thoracic sympathetic chain ganglia provide an additional and substantial efferent supply to the spleen. Cutting of the splenic nerve prevented retrograde labeling of cell bodies in the celiac-mesenteric plexus ganglia and sympathetic chain ganglia of rats injected with tracers into the spleen and also eliminated catecholamine histofluorescence in the spleen. In terms of afferent labeling, the results with FGo indicated that there were no cell bodies labeled in afferent ganglia following splenic injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidines

Reflex changes induced by clonidine in spinal cord injured patients.

In a single blind study of 6 spinal cord injured (SCI) men, the effects of clonidine, a selective alpha-2 adrenergic agonist, on spasticity were compared to diazepam and placebo. Since a potential side-effect of clonidine is postural hypotension, a combination of clonidine and desipramine was also tested. Vibration of the leg will inhibit the H reflex in a normal subject; whereas, this inhibition is markedly reduced in SCI patients with spasticity. A vibratory inhibition index (VII) was derived for each treatment. The pre-treatment VII was 92.08 +/- 3.15%; for SCI subjects, compared to 46.5 +/- 7.7% for 6 normal subjects. Clonidine significantly reduced the mean index of SCI patients to 59.42 +/- 3.91% (p less than 0.001). The VII for placebo, diazepam and the clonidine-desipramine combination were not statistically different than the pre-treatment values in SCI patients. In conclusion, clonidine has an anti-spasticity effect in SCI patients, both subjectively, and objectively, in terms of vibratory inhibition of the H reflex.

Adrenergic alpha-Agonists

Afferent fibers in the reproductive system and pelvic viscera of female rats: anterograde tracing and immunocytochemical studies.

Innervation of the female reproductive system provides an important signal for a variety of neuroendocrine reflexes and behaviors in the female rat. Although some studies suggest that afferent feedback from the gonads is involved in the hypothalamic control of gonadal function and pituitary hormone release, the extent and function of afferent feedback from the gonads in these neuroendocrine reflexes has yet to be clarified. Deafferentation studies have provided only partial support for the afferent control of the gonads. Some studies even suggest functional asymmetries in the neural control of the gonads, but knowledge regarding the neuroanatomical substrate for these possible neurogonadal interactions remains incomplete. Studies with retrograde tract tracers indicate that the ovaries receive a substantial afferent supply from lower thoracic-upper lumbar dorsal root ganglia. Despite stringent precautions to prevent diffusion of tracers following injections into the ovary or related nerves, many of the retrogradely labeled cell bodies identified by these studies may represent an overestimation of the extent of afferent innervation. We have reexamined the afferent innervation of the female reproductive tract by means of the anterograde transport of horseradish peroxidase (HRP) from thoracic, lumbar and sacral dorsal root ganglion to pelvic visceral organs and have studied the effects of unilateral ganglionectomy on substance P containing fibers in the ovary, oviduct and uterus. The neuroanatomical results show that the T13 and L1 dorsal root ganglia provide major afferent innervation to the cranial portion of the reproductive tract and the L6 and S1 dorsal root ganglia provide primary afferent fibers to the caudal portion of the reproductive tract as well as the bladder, rectum and perineum.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways

Double-labeling of neuropeptide Y-immunoreactive neurons which project from the geniculate to the suprachiasmatic nuclei.

A projection from the ventral geniculate area to the suprachiasmatic nuclei (SCN) has been demonstrated in rats and hamsters. Large lesions in this area of the geniculate cause a dramatic decrease in neuropeptide Y-immunoreactivity in the SCN. Since numerous neuropeptide Y-immunoreactive neurons are found in the lateral geniculate area, we and others proposed that these immunoreactive neurons project to the SCN. In the present study, neurons in the lateral geniculate area of golden hamster brains were examined for both neuropeptide Y-immunoreactivity and a retrograde tracer transported from the SCN. Two days after a pressure injection of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the SCN of hamsters, labeled neurons were found in the intergeniculate leaflet and in the external lamina of the anterior ventral lateral geniculate nucleus (VLGN). These neurons were compared with similarly located neurons which showed immunoreactivity for neuropeptide Y. Morphometric comparisons of neuropeptide Y- and WGA-HRP-labeled neurons indicated that they were comparable in terms of soma size, number of dendrites, orientation and location. In additional hamsters, neurons double-labeled with a retrograde tracer and neuropeptide Y-immunoreactivity were localized in the intergeniculate leaflet and in the external lamina of the anterior VLGN. These results demonstrate that many neuropeptide Y-immunoreactive neurons located in both the intergeniculate leaflet and in the external lamina of the anterior VLGN project to the SCN in hamsters.

Animals

Distribution of neuropeptide-like immunoreactivity in intact and chronically decentralized middle cervical and stellate ganglia of dogs.

Neuropeptide-like immunoreactivity to antisera raised against Leu- and Met-enkephalin, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and substance P (SP) have been studied immunohistochemically in middle cervical and stellate ganglia of dogs. To investigate the relationship of the peptides to one another as well as to preganglionic and postganglionic neurons, intact and chronically decentralized middle cervical and stellate ganglia were studied. Ganglia were processed for immunohistochemistry in unoperated dogs and in dogs two weeks after unilateral ganglionic decentralization. The immunoreactivity for each peptide had a characteristic distribution in the ganglia. These distributions differed from one another and from the distribution of cardiac postganglionic sympathetic neurons. Camera lucida drawings of peptide distributions were made to compare different peptides and counts were made to determine the percentages of cells immunoreactive for a given peptide. The results demonstrated that enkephalin-like immunoreactivity in axons was present in both the stellate and middle cervical ganglia, but was heaviest in the caudal 2/3 of the stellate ganglia. Enkephalin-like immunoreactive fibers formed pericellular baskets around stellate ganglion neurons. VIP-like immunoreactive cell bodies and processes were distributed sparsely, but widely, in the stellate ganglia and to a lesser extent in the middle cervical ganglia. One of two commercial antisera to SP resulted in immunoreactive staining of cell bodies and processes in the stellate ganglia. SP-like immunoreactivity in neurons represented about 10% or less of the cells in the stellate ganglia. At least 80-85% of the neurons in the stellate and middle cervical ganglia were immunoreactive for NPY antisera. Decentralization eliminated enkephalin-like immunoreactive staining in the middle cervical and stellate ganglia, but not the VIP-, NPY- and SP-like immunoreactive staining of neurons in these ganglia. In summary, the enkephalin-like immunoreactive axons in the thoracic autonomic ganglia appear to be derived from extrinsic neurons, most likely from preganglionic spinal neurons. VIP-, SP- and NPY-like immunoreactivity were not significantly affected by decentralization. The results provide anatomical evidence for substrates related to neuropeptidergic synaptic mechanisms in thoracic autonomic ganglia.

Animals

Neuroendocrine and behavioral effects of intrathecal capsaicin in adult female rats.

Neural feedback from the gonads and the reproductive tract has an integral role in normal reproductive function in female rats. To further assess the role of sensory feedback in neuroendocrine control, the effects of an intrathecal injection of the neurotoxin, capsaicin (100-125 micrograms) into the lumbosacral region of the spinal cord on reproductive function was tested in female rats. In addition, the effects of capsaicin on the response to noxious heat and pressure were tested. Intrathecal capsaicin had no effect on estrous cycles, ovarian compensatory hypertrophy or female sexual behavior. However, capsaicin treated animals showed a dramatic reduction in fertility, relative to vehicle treated control rats and this was shown to be due to the reduced capacity of vaginal/cervical stimulation to produce pseudopregnancy. Consistent with a selective loss in the effectiveness of cervical stimulation, immobilization produced by vaginal probing was reduced in capsaicin treated rats, but this response slowly recovered across time in some animals. Similarly, the ability of vaginal probing to induce a lordotic response during estrogen treatment was reduced in the capsaicin treated animals. The capsaicin treated animals showed analgesia to noxious heat, as measured by the tail flick test, but showed a normal foot withdrawal in response to pressure. The analgesic effect of vaginal stimulation on noxious pressure was unaltered in the capsaicin treated rats. Finally, the neurotoxic effect of capsaicin was verified in terms of a quantitative reduction in substance P immunoreactivity in the dorsal horns of the lumbosacral region of the spinal cord of capsaicin treated rats, relative to control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Laminar distribution of GABA-immunoreactive neurons and processes in area 18 of the cat.

Intracortical inhibition mediated by the neurotransmitter gamma-amino butyric acid (GABA) plays a crucial role in the formation of the physiological response properties of neurons in mammalian visual cortex. Using a potent antibody developed against the amino acid neurotransmitter. GABA (Immunoclear Co., USA), we have identified GABA-immunoreactive neuronal somata and processes in area 18 of the cat. The GABA-positive neurons included multipolar, bipolar and bitufted but not pyramidal cell types. The density of GABA-immunoreactive neurons was higher in Layers I-IV (range 182-205 cells/mm2) than in Layers V-VI (range 78-92 cells/mm2). The mean areal measurement of GABA-immunoreactive somatic profiles was 135 micron2 (s.d. = 66). We observed numerous GABA-immunoreactive fiber fragments predominantly in Layers I, III, IV and V. Most of the fibers were oriented with their long axis tangential to the cortical surface, but, vertically-oriented fibers were observed as well. Many of the fibers were axonal-like and appeared beaded in Layer I and occasionally in II, while most of the fibers in the other layers appeared myelinated. A dense GABA-immunoreactive neuropil was present in Layer V. Results from our studies provide immunohistochemical evidence for a system of GABA-immunoreactive neurons and axonal collaterals which presumably mediate inhibition in the visual cortex. Since many of the GABA-immunoreactive fibers were oriented tangential to the cortical surface, the structural elements required for inhibition between functional columns are present. GABA-mediated inhibition both within and between functional columns likely assists in the formation of receptive field properties in the visual cortex.

Animals

Female sexual behavior in the golden hamster following kainic acid lesions in the lateral septal area.

Patterns of female sexual behavior in the hamster are qualitatively different from that observed in the rat. Hamsters demonstrate tonic immobility and a sustained lordotic response that can last for several minutes following minimal stimulation from the male while in rats, the lordotic response is highly dependent upon continued stimulation from the male and lasts for only a few seconds following a mount or intromission. Also, the hamster requires both estrogen and progesterone priming in order to display female sexual behavior but the rat can show lordotic behavior following treatment with estrogen alone. Electrolytic lesions in the lateral septal area of female rats produce a facilitation in female sexual behavior and increase behavioral sensitivity to estrogen. However, lesions in the lateral septal area of rats produced by the neurotoxin kainic acid (KA) result in deficits in female sexual behavior following estrogen and progesterone treatment. Given these species differences in sexual behavior, we have examined the effects of KA lesions in the lateral septal area of hamsters on female sexual behavior. Adult female golden hamsters were ovariectomized and tested for female sexual behavior prior to receiving brain surgery. For all behavior tests, animals were injected SC with 60 micrograms of estradiol benzoate/kg per day for two days and 0.5 mg of progesterone three hours prior to the behavior test on day three. Behavior tests consisted of placing the test animal in a male's home cage for 10 minutes and recording the latency to the first lordosis, length of the longest single bout of lordosis and total lordosis duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Re-investigation of the innervation of the thymus gland in mice and rats.

Central to the postulated relationship between the brain and the immune system has been evidence for the direct neural innervation of primary organs of the immune system. It has been reported previously that the thymus gland in rats and mice receives a substantial innervation from the "retrofacial" nucleus of the brain stem and ventral horn cells of the upper cervical spinal cord. Based on the proximity of the thymus to thoracic viscera and neck musculature known to receive motor fibers from these same areas of the brain stem and spinal cord, we examined the possibility that retrogradely labeled cells in the brain stem and spinal cord following injections of tracers into the thymus are due to spread of tracer into the esophagus and neck musculature. Small injections (0.5-2.0 microliter) of wheatgerm agglutinin-horseradish peroxidase (WGA-HRP) were made into the thymus, the esophagus, and the longus colli muscle of rats or mice. Also, the effects of a unilateral cervical vagotomy on cholinesterase activity in the thymus were examined. Finally, the source of the sympathetic supply to the thymus and the presence of catecholamine and cholinesterasic fibers in the thymus was reassessed. Injections of WGA-HRP into the thymus produced little or no labeling in the brain stem and spinal cord. In contrast, control injections into the esophageal wall resulted in numerous intensely labeled cells in the compact formation of the nucleus ambiguus, irrespective of the rostral-caudal level of the esophageal injection. Similarly, tracer injections into the longus colli muscle resulted in numerous intensely labeled cells in the ventral horn of the upper cervical spinal cord. Unilateral vagotomy did not alter cholinesterase activity in the thymus even though it was largely depleted in the ipsilateral nucleus ambiguus. The histochemical studies verified a major sympathetic innervation of the thymus gland. In keeping with this result, in animals in which no labeled cells were observed in the brain stem or spinal cord following thymus injection, labeled cells were, however, observed in the sympathetic chains from the superior cervical ganglia caudal to the T3 ganglia. In summary, all labeled cells in the brain stem and cervical spinal cord observed following tracer injections into the thymus can be accounted for by spread of the tracer into surrounding structures, leading to spurious labeling.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

The effects of lesions in the lateral septal and hippocampal areas on the humoral immune response of adult female rats.

There are interactions between the immune and the endocrine systems. A major role for adrenal steroids in the modulation of the immune system is well documented and the immune system can apparently activate the adrenal axis at the hypothalamic and/or pituitary level. Sex steroids modify immune function and sex differences in immune function suggest that there are also major interactions between the reproductive system and the immune system. To the extent that the endocrine system is integrated with the immune system, many of the brain areas and neural mechanisms implicated in psychoneuroendocrine processes may be involved in the regulation of psychoneuroimmune processes. We have proposed that the septal region represents an important extrahypothalamic and now propose that the septal region may also represent an important component in the central regulation of psychoneuroimmune processes. We have tested the effects of electrolytic and kainic acid (KA) lesions in the lateral septal area of female rats and have compared the effects of KA lesions in the lateral septal area with KA lesions in the hippocampal region on antibody production following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant. Blood samples were collected on Days 0, 7, 14, 17, and 28 following immunization in the first experiment and on Days 0, 7, 14, and 28 in the second study. All animals were injected again with ovalbumin on Day 14. The IgG, IgA, and IgM antibody titers were then measured by an enzyme-amplified ELISA assay. KA lesions in the lateral septal area produced extensive cell loss in this region and produced a concurrent loss of cell bodies in the CA 3-CA 4 hippocampal areas. Compared to sham and electrolytic septal lesioned rats, KA lesions of the lateral septal area significantly reduced IgG titers on Days 7 and 17 with a trend for Day 14. Similarly, the IgA and IgM titers were significantly lower on Days 7, 14, and 17 for the rats with KA lesions in the lateral septal area. In addition, the KA septal lesioned rats gained more body weight and had higher thymus weights, relative to the electrolytic lesioned and sham groups. In addition, the rats with KA lesions in the hippocampal area showed significantly higher IgM titers on Day 7, elevated IgG titers on Day 14, and lower IgA titers on Day 28, relative to the sham group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Neuroestrogenic control of feeding behavior and body weight in rats with kainic acid lesions of the lateral septal area.

The role of the lateral septal area (LS) in the regulation of energy balance and the estrogenic control of feeding behavior in the female rat has been examined. Food intake (FI) and body weight (BWt) were measured daily following kainic acid (KA) LS lesions (KALS) to assess any regulatory changes in energy balance. In all animals KA lesions of the LS produced major cell loss in the LS; however the extent of damage was variable. Associated with KA lesions of the LS was the concurrent loss of CA3-CA4 cell groups in the hippocampus which was comparable for all the lesioned animals. The extent of septal damage was quantified morphometrically and correlated with changes in FI and BWt following estrogen treatment. The significant effects of the KALS lesions, relative to the control animals were: an increase in BWt which was statistically significant 22 days following brain surgery, an increase in daily FI which was significant by day 6 post surgery, an attenuation in the anorexic effects of estrogen on FI and BWt, and a significant decrease in the present days of vaginal estrus. Moreover, the anorexic effects of estrogen were significantly correlated with the extent of LS damage, but not the amount of hippocampal damage. The present study confirms that an increase in BWt is produced by KA lesions of the LS and further indicates that a sustained period of increased FI precedes the increase in BWt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Differential effects of neurotoxic lesions on psychoneuroendocrine functions.

The use of neurotoxic agents has provided new insight into the functions of the septal region. The psychoneuroendocrine effects of kainic acid (KA) lesions in the lateral septum (LS) have been confirmed, and we have compared the effects of these lesions to those following lesions of the medial septum (MS) and hippocampus (HP). In addition, the effects of the cytotoxin ibotenic acid (Ibo), have been studied. The alterations in psychoneuroendocrine functions resulting from the cytotoxic lesions have been compared to those from electrolytic septal lesions (DCLS) and sham operations. KA and Ibo lesions of the LS resulted in extensive bilateral loss of neurons in the LS; however, KALS lesions also resulted in cell loss in the CA3-CA4 cell regions of the HP. In contrast, KA and Ibo lesions of the MS did not produce any obvious cell loss in the MS. KA lesions of the HP produced extensive CA3-CA4 cell loss and a reduction in the size of the fornix and rostral septum. The behavioral and endocrine effects of these lesions were, relative to controls: the KALS group exhibited fewer percent days of vaginal estrus, increased ovarian compensatory hypertrophy (OCH), increased body weight (BWt), attenuation in the anorexic effects of estrogen, and decreased female sexual behavior. The KAMS group exhibited a transitory increase in BWt and increased male sexual behavior. IboLS group demonstrated a greater percent days of vaginal estrus and increased female sexual behavior whereas the IboMS group exhibited a decrease in OCH. The KAHP group exhibited a partial attenuation in the anorexic effects of estrogen on food intake and BWt gain. The DCLS group demonstrated increased female sexual behavior. These results indicate that the septal region is involved in both facilitatory and inhibitory modulation of a variety of estrogen responsive processes and further suggest that the MS and LS have different psychoneuroendocrine functions.

Animals

Non-overlapping thalamocortical projections for separate forepaw digits before and after cortical reorganization in the raccoon.

The fluorescent dye retrograde tracing technique was used to examine the projection from ventroposterior lateral thalamus to primary somatosensory cortex in the raccoon. Results are presented from fifteen experiments using Fast Blue in combination with either Nuclear Yellow or Diamidino Yellow Dihydrochloride. Injections of two dyes into adjacent but separate digit regions of cortex produced single-labeling of thalamic neurons, suggesting that projections for each digit are separate and independent with no branching to adjacent parts of the somatotopic map. Double-labeling was only seen when the cortical injection sites were overlapping. Similar results were seen in six cases in which amputation of the 5th digit of the contralateral forepaw was carried out four months earlier. These results suggest that neither the strengthening of existing collaterals nor growth of new collaterals in the thalamocortical projection are likely to be responsible for the physiological reorganization that is seen in raccoon cortex after peripheral deafferentation.

Amputation, Surgical