Biomedical subjects

Judy K Brunso-Bechtold

Publications and source records attributed to Judy K Brunso-Bechtold.

9 recordsLinked to original sources

PubMed2006

Synaptogenesis in the inferior colliculus of the pre-hearing postnatal ferret.

Although intrinsic organization in the inferior colliculus (IC) has been surveyed in a variety of species, current knowledge of synaptogenesis within the mammalian inferior colliculus is limited. The present study surveyed the ultrastructure of the central nucleus of the inferior colliculus in postnatal day (P) P4, P7, P14, and P28 ferrets, prior to the onset of hearing at the end of the first postnatal month with the goal of beginning to characterize the time course of synapse formation in relation to the development of afferent projection patterns within the IC. Results suggest that initial synaptogenesis has occurred in the IC by P4 and continues during the period when maturation of the distribution of axons from brainstem auditory nuclei is taking place.

Animals↗

PubMed2006

Growth hormone and IGF-I modulate local cerebral glucose utilization and ATP levels in a model of adult-onset growth hormone deficiency.

Decreases in plasma IGF-I levels that occur with age have been hypothesized to contribute to the genesis of brain aging. However, support for this hypothesis would be strengthened by evidence that growth hormone (GH)/IGF-I deficiency in young animals produces a phenotype similar to that found in aged animals. As a result, we developed a unique model of adult-onset GH/IGF-I deficiency by using dwarf rats specifically deficient in GH and IGF-I. The deficiency in plasma IGF-I is similar to that observed with age (e.g., 50% decrease), and replacement of GH restores levels of IGF-I to that found in young animals with normal GH levels. The present study employs this model to investigate the effects of circulating GH and IGF-I on local cerebral glucose utilization (LCGU). Analysis of LCGU indicated that GH/IGF-I-deficient animals exhibit a 29% decrease in glucose metabolism in many brain regions, especially those involved in hippocampally dependent processes of learning and memory. Similarly, a high correlation between plasma IGF-I levels and glucose metabolism was found in these areas. The deficiency in LCGU was not associated with alterations in GLUT1, GLUT3, or hexokinase activity. A 15% decrease in ATP levels was also found in hippocampus of GH-deficient animals, providing compelling data that circulating GH and IGF-I have significant effects on the regulation of glucose utilization and energy metabolism in the brain. Furthermore, our results provide important data to support the conclusion that deficiencies in circulating GH/IGF-I contribute to the genesis of brain aging.

Adenosine Triphosphate↗

PubMed2006

Spatial learning and memory deficits after whole-brain irradiation are associated with changes in NMDA receptor subunits in the hippocampus.

Whole-brain irradiation is used for the treatment of brain tumors, but can it also induce neural changes, with progressive dementia occurring in 20-50% of long-term survivors. The present study investigated whether 45 Gy of whole-brain irradiation delivered to 12-month-old Fischer 344 x Brown Norway rats as nine fractions over 4.5 weeks leads to impaired Morris water maze (MWM) performance 12 months later. Compared to sham-irradiated rats, the irradiated rats demonstrated impaired MWM performance. The relative levels of the NR1 and NR2A but not the NR2B subunits of the NMDA receptor were significantly higher in hippocampal CA1 of irradiated rats compared to control rats. No significant differences were detected for these NMDA subunits in CA3 or dentate gyrus. Further analysis of CA1 revealed that the relative levels of the GluR1 and GluR2 subunits of the AMPA receptor and synaptophysin were not altered by whole-brain irradiation. In summary, a clinically relevant regimen of fractionated whole-brain irradiation led to significant impairments in spatial learning and reference memory and alterations in the relative levels of subunits of the NMDA, but not the AMPA, receptors in hippocampal CA1. These findings suggest for the first time that radiation-induced cognitive impairments may be associated with alterations in glutamate receptor composition.

Animals↗

PubMed2005

Quantitative changes in calretinin immunostaining in the cochlear nuclei after unilateral cochlear removal in young ferrets.

Neurons of the cochlear nuclei receive axosomatic endings from primary afferent fibers from the cochlea and have projections that diverge to form parallel ascending auditory pathways. These cells are characterized by neurochemical phenotypes such as levels of calretinin. To test whether or not early deafferentation results in changes in calretinin immunostaining in the cochlear nucleus, unilateral cochlear ablations were performed in ferrets soon after hearing onset (postnatal day [P]30-P40). Two months later, changes in calretinin immunostaining as well as cell size, volume, and synaptophysin immunostaining were assessed in the anteroventral (AVCN), posteroventral (PVCN), and dorsal cochlear nucleus (DCN). A decrease in calretinin immunostaining was evident ipsilaterally within the AVCN and PVCN but not in the DCN. Further analysis revealed a decrease both in the calretinin-immunostained neuropil and in the calretinin-immunostained area within AVCN and PVCN neurons. These declines were accompanied by significant ipsilateral decreases in volume as well as neuron area in the AVCN and PVCN compared with the contralateral cochlear nucleus and unoperated animals, but not compared with the DCN. In addition, there was a significant contralateral increase in calretinin-immunostained area within AVCN and PVCN neurons compared with control animals. Finally, a decrease in area of synaptophysin immunostaining in both the ipsilateral AVCN and PVCN without changes in the number of boutons was found. The present data demonstrate that unilateral cochlear ablation leads to 1) decreased immunostaining of the neuropil in the AVCN and PVCN ipsilaterally, 2) decreased calretinin immunostaining within AVCN and PVCN neurons ipsilaterally, 3) synaptogenesis in the AVCN and PVCN ipsilaterally, and 4) increased calretinin immunostaining within AVCN and PVCN neurons contralaterally.

Animals↗

PubMed2005

Caloric restriction does not reverse aging-related changes in hippocampal BDNF.

Caloric restriction (CR) can attenuate the aging-related decline in learning and memory in rats. Understanding the mechanisms underlying this effect could lead to therapies for human memory impairment. We tested the hypotheses that aging is associated with a decline in hippocampal brain-derived neurotrophic factor (BDNF), a growth factor that enhances learning and memory, and that CR increases hippocampal BDNF. We compared BDNF protein levels in hippocampal subregions of young, middle-aged and old rats fed CR or ad libitum (AL) diets. Mean BDNF levels in the dentate gyrus and CA3 did not differ with diet but increased with age. In CA1, BDNF levels were slightly higher in CR than AL rats at middle and old age but did not change across lifespan. These data suggest that mnemonic impairments with age do not reflect a decrease in hippocampal BDNF. Furthermore, if CRs attenuation of aging-related memory changes is mediated by BDNF, then it must be through a small, CA1-specific increase and does not involve reversal of an aging-related decline in BDNF.

Age Factors↗

PubMed2004

Alterations in calretinin immunostaining in the ferret superior olivary complex after cochlear ablation.

In this study, we used image analysis to assess changes in calretinin immunoreactivity in the lateral (LSO) and medial (MSO) superior olivary nuclei in ferrets 2 months after unilateral cochlear ablations at 30-40 days of age, soon after hearing onset. These two nuclei are the first significant sites of binaural convergence in the ascending auditory system, and both receive direct projections from the deafferented cochlear nucleus. Cochlear ablation results in a decrease in the overall level of calretinin immunostaining within the LSO ipsilaterally compared with the contralateral side and with control animals and within the MSO bilaterally compared with control ferrets. In addition, the level of calretinin immunostaining ipsilaterally within neurons in the LSO was significantly less in cochlear ablated than control animals. In contrast, there was no effect of cochlear ablation on the level of calretinin immunostaining within neurons either in the contralateral LSO or in the MSO. These results are consistent with a downregulation in calretinin within the neuropil of MSO bilaterally and LSO ipsilaterally, as well as a downregulation in calretinin within somata in the ipsilateral LSO as a result of unilateral cochlear ablation soon after hearing onset. Thus, cochlear-driven activity appears to affect calcium binding protein levels in both neuropil and neurons within the superior olivary complex.

Animals↗

PubMed2003

Upregulation of calretinin immunostaining in the ferret inferior colliculus after cochlear ablation.

In many systems, including ascending auditory pathways, calcium-binding proteins are markers of specific neuronal circuits. Previous studies suggest that calretinin immunostaining may be a specific marker for circuits in the inferior colliculus (IC) that code timing information. We undertook experiments to determine the changes in calretinin immunostaining in the IC that take place in response to cochlear ablation. Cochlear ablation was performed unilaterally in ferrets just after hearing onset. Animals survived for 2-3 months after ablation and brains were then processed for calretinin immunocytochemistry. The mean optical density and stained area of the calretinin immunopositive plexus in the IC were determined for five coronal sections through the right and left IC. In controls (n = 3), measurements of these parameters in the central nucleus of the IC showed symmetry between the two sides. In experimental animals (n = 8) the calretinin immunopositive plexus contralateral to the cochlear ablation was denser and larger than that in either the ipsilateral IC or in the IC of control animals. The calretinin plexus in the ipsilateral IC was slightly less dense and smaller than in controls but the differences did not reach statistical significance. IC volume measurements and synaptophysin immunostaining analysis in the central nucleus of the IC revealed no statistical differences between ablated and control animals or between the two sides in ablated animals. The significant increase in both mean optical density and immunostained area of the calretinin plexus in the IC contralateral to the cochlear ablation may reflect an upregulation in calretinin expression in the nuclei that contribute to this plexus.

Animals↗

PubMed2003

Quantitative measurement of afferent layers in the ferret inferior colliculus: DNLL projections to sublayers.

In the central nucleus of the inferior colliculus (IC), afferent projections are aligned with dendritic arbors of disk-shaped cells, forming fibrodendritic layers. One feature that may serve as a guide for study of the intrinsic organization of the IC layers is the segregation of certain inputs to bands and patches within the layers of the central nucleus. In this study, we used Phaseolus leucoagglutinin as an anterograde tracer to examine the projections from the dorsal nucleus of the lateral lemniscus to the contralateral IC in adult ferrets. The labeled afferent projections distributed along the IC layers in a series of bands where there were dense endings and interband spaces where there were few if any endings. Branches of individual labeled axons that were reconstructed distributed within a single afferent band. Measurements of both the terminal density distribution and the optical density across the band were similar indicating that afferent bands were approximately 85 microm thick. Quantitative measurements of the labeled afferent bands will enhance comparison with other afferent projections and analysis of afferent development and plasticity.

Animals↗

PubMed2002

Insulin-like growth factor-1 does not ameliorate the age-related decline in presumptive inhibitory synapses in layer 2 of rat sensorimotor cortex.

Four old (29 months) Brown Norway x Fischer 344 (BN x F344) rats received intracerebroventricular infusion of insulin-like growth factor-1 (IGF-1) and four middle-aged (18 months) and four old (29 months) rats received infusion of saline for 28 days. Sensorimotor cortex containing layer 2 was blocked and processed for electron microscopy. Thin (700 A) and semithin (1 microm) sections were collected from the same anatomical space for quantification of synapses and neurons, respectively, using the physical disector. Numerical density (Nv) of presumptive inhibitory synapses in layer 2 of sensorimotor cortex has been reported to decline with age Poe et al., 2001; Brunso-Bechtold et al. [Brain Res. 872 (2000) 125]. Infusion of IGF-1 did not affect the density of synapses or neurons when old IGF-1 animals were compared with old saline animals.

Aging↗