Biomedical subjects

M F Montaron

Publications and source records attributed to M F Montaron.

At least 19 recordsLinked to original sources

PubMed2005

Lifelong corticosterone level determines age-related decline in neurogenesis and memory.

Ageing is accompanied by an alteration of spatial memory, a decline in hippocampal neurogenesis and a dysregulation of the hypothalamic-pituitary axis (HPA) leading to elevated levels of circulating corticosterone. However, the role of the HPA axis in age-related decline in cognitive functions and in neurogenesis decline remains unclear. We found that suppression of glucocorticoids secretion from midlife to the rest of the animals' life increases neurogenesis in old animals and prevents the emergence of age-related memory disorders. Reciprocally, aged rats with a chronic upregulation of the HPA axis exhibit not only spatial memory impairments but also very low levels of hippocampal cell proliferation and survival. Altogether, these results indicate that the extent of lifetime exposure to glucocorticoids determines the extent of age-related decline in hippocampal neurogenesis and consequently age-related cognitive dysfunctions.

Adrenal Glands↗

PubMed2004

Environmentally induced long-term structural changes: cues for functional orientation and vulnerabilities.

Environmental challenges profoundly modify phenotypes and disrupt inherent developmental programs both at functional and structural levels. As an example, we have studied the impact of these environmental influences on adult neurogenesis in the dentate gyrus. Neurogenesis results from an inherent program, participates to hippocampal network organization and, as a consequence, to the various functional abilities depending on this region, including memories. In preclinical studies of aging we have shown that phenotypes vulnerable to the development of spatial memory disorders are characterized by lower hippocampal neurogenesis. We have hypothesized that these interindividual variations in functional expression of neurogenesis in senescent subjects could be predicted early in life. Indeed, a behavioral response (novelty-induced locomotor reactivity) and a biological trait (hypothalamo-pituitary-adrenal axis activity), which are predictive of cognitive impairments later in life, are related to neurogenesis in young adult rats. This suggests that subjects starting off with an impaired neurogenesis, here rats that are high reactive to stress, are predisposed for the development of age-related cognitive disorders. We have further shown that these inter-individual differences result from early deleterious life events. Indeed, prenatal stress orients neurogenesis in pathological ways for the entire life, and precipitates age-related cognitive impairments. Altogether these data suggest first that hippocampal neurogenesis plays a pivotal role in environmentally-induced vulnerability to the development of pathological aging, and second that environmental challenges and life events orient structural developments, leading to different phenotypes.

Animals↗

PubMed2003

Implication of corticosteroid receptors in the regulation of hippocampal structural plasticity.

The dentate gyrus is one of the few areas of the adult brain that continues to produce neurons and to express the embryonic polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM). The stress hormone corticosterone exerts a complex modulation on neurogenesis and PSA-NCAM, and previous studies have shown that mature granule cells require corticosterone for their survival. Thus, the aim of our work was to investigate the respective role of the different corticosteroid receptors on these three parameters in adrenalectomized rats. It was found that treatment with a low dose of the mineralocorticoid receptor agonist, aldosterone, prevents only the adrenalectomy-induced increase in cell death. Treatment with a higher dose of aldosterone normalized cell proliferation whereas PSA-NCAM expression was normalized only by treatment with the glucocorticoid receptor agonist, RU 28362. It is concluded that stimulation of the mineralocorticoid receptor is sufficient to mediate the effects of corticosterone on neurogenesis and to protect mature cells from cell death whereas stimulation of the glucocorticoid receptor is necessary to modulate PSA-NCAM expression.

Adrenal Cortex Hormones↗

PubMed2000

Influence of environment on the efficacy of intrastriatal dopaminergic grafts.

Functional recovery is influenced by experience. The aim of the present work was to examine the effects of "enriched" environment (EE) versus an "impoverished" environment on the anatomical and functional integration of intrastriatal dopaminergic grafts. These influences were studied using a paradigm where grafting was performed before the dopamine-depleting lesion. Dopaminergic grafts were implanted into the left neostriatum of adult male rats. In the enriched group, grafted rats were housed collectively and were trained on different behavioral tests following grafting. In contrast, impoverished grafted rats were housed individually and not further manipulated. Ten weeks after grafting, the mesotelencephalic dopaminergic pathway was destroyed unilaterally to the grafted side and different behaviors were followed for 7 months. Grafting prior to lesioning had no prophylactic effects on the performance as the graft did not prevent the onset of the lesion-induced impairments. However, under EE conditions, a graft effect was manifested in the reduction of drug-induced rotation and on the indices of bias as tested by a spatial alternation test. No positive graft effects were observed in the skilled paw reaching test. Grafted rats raised under impoverished conditions performed in a fashion indistinguishable from the control lesioned animals on most measures of behavior. A beneficial effect of EE conditions was observed on survival of TH-positive neurons within the grafts. The results suggest that survival of grafted neurons, and the reduction of the magnitude of particular behavioral impairments, can be optimized by increasing the complexity of the subject's environment.

Animals↗

PubMed1999

Effects of amphetamine and cocaine treatment on c-Fos, Jun-B, and Krox-24 expression in rats with intrastriatal dopaminergic grafts.

Activation of dopaminergic (DA) transmission by psychostimulants increases c-fos expression. d-Amphetamine-induced c-fos activation is reduced in the neostriatum deprived of DA afferents. Dopaminergic grafts implanted into the denervated neostriatum induce a c-fos hyperexpression when challenged with d-amphetamine, which is correlated with the exaggerated compensation of d-amphetamine-induced rotation. The aim of the present study was to test the generality of this phenomenon and the effects of DA grafts on the expression of three immediate early gene-coded proteins (c-Fos, Jun-B, Krox-24) following a challenge with either d-amphetamine or cocaine. c-fos basal expression was low in the neostriatum and was increased by the administration of psychostimulants. These effects were blocked by the DA lesion and restored by the DA grafts. A c-fos hyperexpression was observed within the grafted neostriatum, which was correlated with the compensation of d-amphetamine- or cocaine-induced rotation. Basal levels of Jun-B- and Krox-24-LI nuclei were high within the neostriatum. Administration of d-amphetamine or cocaine did not influence the expression of these IEG-coded proteins. Jun-B expression was not affected by the surgical procedure. In contrast, lesion of DA afferents of neostriatum decreased Krox-24 basal expression, an effect reversed by the grafts. Thus, the expression of c-fos but not Jun-B or Krox-24 appeared to be a good marker for the rotational behavior exhibited by DA-grafted rats challenged with drugs that increased DA transmission. This generalized c-fos overshoot indicates an abnormal activation of postsynaptic neurons by dopamine and points to its value as an indicator of the deleterious effects of DA grafts.

Animals↗

PubMed1999

Adrenalectomy increases neurogenesis but not PSA-NCAM expression in aged dentate gyrus.

Ageing is accompanied by a decline in neurogenesis and in polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) expression within the hippocampus and by elevated basal levels of circulating corticosterone. In a companion study, we demonstrated that suppression of corticosterone by adrenalectomy increased neurogenesis and PSA-NCAM expression in the dentate gyrus of adult rats. Here we show that adrenalectomy increased neurogenesis in this structure in old rats, as measured by the incorporation of 5-bromo-2'-deoxyuridine in neuronal progenitors. This effect was prevented by corticosterone replacement. In contrast, PSA-NCAM expression remained unchanged in comparison with controls. Thus, in the aged brain, stem cells are still present and able to enter the cell cycle. This may point to ways of protecting or treating age-related cognitive impairments.

Adrenal Glands↗

PubMed1999

[Corticosteroid hormones and the brain].

The anatomical and functional links between the hormone stress axis and the cortico-limbic brain regions which integrate emotion and motivation are well documented. It is important, considering the consequences of stress on the brain, to take into account the regulatory buffer capacities of the personality-cognitive processes. Another point of interest is evaluation of the long term effects of repeated life events on chronic environmental pressures which induce brain negative feedback defects and, subsequently, insidious cellular changes in regions such as the hippocampus that lead to memory or adaptive impairments. An example is provided by perinatal stress that induces, later in life, both hormonal and cognitive deleterious changes.

Adrenal Cortex Hormones↗

PubMed1998

Behavioural recovery after unilateral lesion of the dopaminergic mesotelencephalic pathway: effect of repeated testing.

Functional recovery following a complete unilateral lesion of the nigrostriatal pathway in adult rats was studied. We examined the effect of training on the spontaneous or induced postural bias following the lesion. Two tasks measuring lateralization were used to assess the lesion-induced postural bias: spontaneous asymmetry was evaluated in the Y-maze, whereas induced body bias was measured by hanging the rat by its tail. Recovery was assessed at three different times following the lesion. The effects of lesion in adult rats in the short, medium and long term were evaluated and compared with the effects of dopaminergic transplants. In adult lesioned rats, destruction of dopaminergic innervation of the neostriatum induced initially an ipsilateral bias as measured in the "tail hang test" and the Y-maze. Recovery of function was observed in the tail hang test as ipsilateral bias declined on repeated testing. Apart from this effect, there was a post-lesion interval effect, since the postural bias disappeared more rapidly on repeated testing in the long-term lesioned rats. This spontaneous recovery was impaired by intrastriatal dopaminergic grafts. Furthermore, no spontaneous recovery was observed in the Y-maze test. These observations show that repeated testing can influence the long-term effects of damage to the nigrostriatal dopamine system.

Animals↗

PubMed1998

Complex regulation of the expression of the polysialylated form of the neuronal cell adhesion molecule by glucocorticoids in the rat hippocampus.

The gyrus dentatus is one of the few areas of the brain that continues to produce neurons after birth. The newborn cells differentiate into granule cells which project axons to their postsynaptic targets. This step is accompanied by the transient expression of the polysialylated isoforms of neuronal cell adhesion molecules (PSA-NCAM) by the developing neurons. Glucocorticoid hormones have been shown to inhibit neurogenesis. We noted a functional correlation between PSA-NCAM expression and glucocorticoid action after manipulation of corticosterone levels in the adrenalectomized rat. Adrenalectomy increased neurogenesis, evaluated from the incorporation of 5-bromo-2'-deoxyuridine in neuronal precursors, as well as PSA-NCAM expression. The increase in PSA-NCAM-immunoreactive (IR) cells in the gyrus dentatus, evidenced 72 h following adrenalectomy, persisted for at least a month. It was accompanied by enhanced dendritic arborization of PSA-NCAM-IR cells in the gyrus dentatus and by an increase in number of PSA-NCAM-IR fibres in the CA3 subfield. Neurogenesis was normalized by restitution of diurnal or nocturnal levels of corticosterone, whereas normalization of PSA-NCAM expression was only observed after simulation of the complete circadian fluctuation of the hormone. Our findings reveal the complex action of corticosterone in modulating the expression of PSA-NCAM in the gyrus dentatus of the hippocampal formation. They also highlight the importance of corticosterone fluctuations in the control of neurogenesis and plasticity in this structure.

Adrenalectomy↗

PubMed1997

Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated.

Age-dependent spatial memory impairments have been related to a decline in hippocampal plasticity. Highly polysialylated neuronal cell adhesion molecules (PSA-NCAM) show a strong expression during adulthood within regions associated with neuroplastic events. Furthermore, NCAM molecules have been proposed to mediate neuronal plasticity during learning and memory. The aim of the present study was to examine the effect of ageing on the expression of PSA-NCAM within the hippocampus. To investigate whether age-dependent changes in expression of PSA-NCAM were accentuated in aged rats with learning impairment, animals were in a first step assessed for their cognitive abilities using a Morris water maze. Seven-month-old and 24-month-old-rats were tested for their performance in the Morris water maze. The animals were sacrificed and brain sections were processed for PSA-NCAM immunohistochemistry. Ageing was accompanied by an overall decrease in PSA-NCAM-immunoreactivity (-IR) within the forebrain, presenting a important decrease of the number of PSA-NCAM-IR perikarya within the hippocampus. These results were confirmed by Western blot analysis. No difference in PSA-NCAM immunoreactivity was observed in aged rats with or without spatial learning impairment. It is concluded that although changes in PSA-NCAM accompanied the decrease in cognitive abilities, our data did not evidence a causal relationship between these two parameters.

Aging↗

PubMed1996

Effect of lesioning the nucleus accumbens on attentive preparation and performance of a reaching movement in the cat.

The nucleus accumbens is often considered as an interface between limbic and motor brain structures. In the present experiment, we investigated the effect of a bilateral lesion of the nucleus accumbens on a motor task with attentional constraints. Four male cats were trained to reach for a mobile target that was only accessible for a short period of time and after a variable delay of expectation. They were food-rewarded. Their visuomotor performance was analyzed in speed and accuracy. Their ECoG was recorded to evaluate the occurrence of beta-rhythms that have been shown to be related to a behaviour of focalized attention. After stabilization of their visuomotor performance, all subjects underwent a bilateral neurotoxic lesion of the nucleus accumbens. After lesion, cats were able to maintain their focalized attention while waiting for the target for longer periods of time and the probability of beta-activity increased. Their visuomotor performance showed an improvement both in accuracy and in speed. Moreover, unexpected external stimuli were less efficient in diverting the cats' attention from their task, so that the proportion of unsuccessful trials due to inattention decreased after lesion. The data showed that the lesion induced a focalization of attention resulting in an improvement of motor performance. The role of the nucleus accumbens both in attention control and in modulating motor output is discussed together with the possible cerebral pathway involved.

Animals↗

PubMed1996

Prefrontal cortex inputs of the nucleus accumbens-nigro-thalamic circuit.

The functional organization of the cortico-nucleus accumbens-substantia nigra pars reticulata circuit was investigated in the rat using combined anatomical and electrophysiological approaches. The nucleus accumbens neurons which project to the substantia nigra pars reticulata are located in a circumscribed region of the core immediately adjacent and extending dorsally to the anterior commissure. As shown by retrograde and anterograde transports of wheatgerm agglutinin conjugated to horseradish peroxidase, the region of the nucleus accumbens related to the substantia nigra was found to receive bilateral inputs from restricted areas of the medial and lateral prefrontal cortex, i.e., prelimbic/medial orbital and dorsal agranular insular areas. The electrical stimulation of these medial and lateral prefrontal cortical areas induced excitatory responses in nucleus accumbens neurons projecting to the dorsomedial substantia nigra pars reticulata. Interestingly, an important proportion (61%) of the nucleus accumbens-nigral cells responding to the stimulation of the lateral prefrontal cortex were also excited by the stimulation of the medial prefrontal cortex, demonstrating the existence of a convergent influence of these cortical areas on single nucleus accumbens cells. Furthermore, the present data also show that the stimulation of the medial prefrontal cortex results in a powerful inhibition of the tonic firing of the substantia nigra pars reticulata neurons. In conclusion, this study reveals the existence of a functional link between the prefrontal cortex (prelimbic/medial orbital and agranular insular areas) and the nucleus accumbens neurons which innervate the dorsomedial region of the substantia nigra pars reticulata. Since the dorsomedial region of substantia nigra pars reticulata is known to project to subfields of the mediodorsal and ventromedial thalamic nuclei related to the prefrontal cortex, the present data further demonstrate the existence of a prefrontal-nucleus accumbens-thalamo-cortical circuit involving the substantia nigra pars reticulata.

Animals↗

PubMed1992

Effects of mediodorsalis thalamic nucleus lesions on vigilance and attentive behaviour in cats.

In this study performed on 10 cats we analysed the effects of limited lesions of nucleus medialis dorsalis of the thalamus (MD) on behaviour and on some specific electrocorticographic (ECoG) patterns, known from previous works to accompany various states of waking attentiveness. The animals were tested during 90 min in three distinct behavioural situations; a neutral one (NS) where they simply explored their environment and then usually went to sleep; a second one (FA) where they could watch a mouse (but not catch it), which favoured 'focussed' attentiveness accompanied by the development of rhythmic ECoG activities in the anterior frontoparietal cortex ('beta rhythms' at 40 Hz); a third one (EX) with a hidden mouse whose appearance the cat was waiting for ('expectancy') which rather than favouring the development of beta rhythms elicited the appearance of another rhythmic activity dominating in somatic area SI, 'mu rhythms' at 14 Hz. The duration of each waking behaviour and its ECoG concomitant as well as that of slow wave and of paradoxical sleep were compared in each cat before and after lesion. Our results showed that MD lesions situated in the posterior part of the nucleus tended to increase the time occupied by focussed attentive behaviour and the accompanying beta rhythms. On the other hand, anteriorly located MD lesions elicited a concomitant reduction of both manifestations, behavioural and electrocortical. No such contrasting effects could be systematically noticed for the durations of expectancy, of slow sleep and of paradoxical sleep. These findings were discussed considering previous data showing that at least two systems project upon MD, that play distinct--in a way even antagonistic--roles in focussed attention upon a target. Both originate from the ventral tegmental mesencephalic area; one reaches MD through the ventral striatum (nucleus accumbens), the other one through the amygdala. The MD nucleus thus receiving contrasting information may participate in a final adjustment of the attentive state of the animal to its environment.

Animals↗

PubMed1992

Cryoblockade in limbic brain (amygdala) prevents or delays ventricular fibrillation after coronary artery occlusion in psychologically stressed pigs.

Neomammalian and paleomammalian (limbic) brain structures control different behaviors and the autonomic support specific to each. Both neural systems are involved in cardiovascular disorders. Our previous studies showed that bilateral cryoblockade of a neomammalian structure (the frontal lobes) reduces blood pressure elevations in experimental hypertension and prevents lethal arrhythmogenesis in experimental myocardial infarction. Other studies showed that bilateral lesions in a paleomammalian structure (amygdala) also reduce the blood pressure elevations. Thus, we hypothesized that cryoblockade of the amygdala would prevent lethal arrhythmogenesis. We found that cooling of cryoprobes implanted bilaterally in the amygdala prevented ventricular fibrillation in five of eight pigs during a 20-minute period of reversible myocardial ischemia, whereas cryoblockade in structures surrounding the amygdala (five pigs), unilateral cryoblockade in the amygdala (two pigs), or sham operations (three pigs) did not prevent ventricular fibrillation (p less than 0.003). In two of the five pigs with amygdaloid blockade, the cooling was reversed at 20 minutes while the coronary occlusion continued (24 hours), and still ventricular fibrillation did not occur. In all other cases, ischemia was reversed at 20 minutes so that the heart could recover; this enabled histochemical documentation that the heart was normal at the time(s) ischemia was induced, and it allowed within-subject control experiments. Amygdaloid cryoblockade produced a small but significant increase in heart rate (10 beats per minute) without a change in blood pressure. We conclude that the paleomammalian brain, like its neomammalian counterpart, mediates brain effects on fatal arrhythmogenesis.

Amygdala↗

PubMed1990

Action of tianeptine on focalization of attention in cat.

Tianeptine, an antidepressant substance devoid of sedative action, was investigated for its effects on focalization of attention in cats, using combined behavioural and electrocorticographic (ECoG) observations. The ECoG index was the presence of 40 Hz frontoparietal rhythmic cortical activities, developing while the animal displayed a behaviour suggesting focused attention. Cats were observed in two conditions: a "neutral" one, with no specific target, and another one, "of focused attention" where a live mouse placed in a transparent box was present in the recording room, each test lasting for 90 min. After treatment the animals displayed increased attention even in the neutral situation, where the cat, instead of sleeping like during control sessions, payed sustained attention to its environment. Conversely, at corresponding doses, amitriptyline, another antidepressant drug chosen as a reference, induced uninterrupted slow sleep even in the situation of focused attention.

Amitriptyline↗

PubMed1988

Relationships between nucleus medialis dorsalis, pericruciate cortex, ventral tegmental area and nucleus accumbens in cat: an electrophysiological study.

In anaesthetized cats, single units were recorded from the ventrolateral part of n. medialis dorsalis (MD) of the thalamus. Cells were tested for their ortho- or antidromic short latency responses to single electrical shocks applied to the pericruciate cortex (PCx) and to either the mesencephalic ventral tegmental area (VTA) or the nucleus accumbens (ACC). Some reciprocal direct connections were thus shown to exist between MD and PCx, i.e. a cortical area posterior to the main classical MD "prefrontal" projection zone. Reciprocal direct connections were also identified physiologically between MD and VTA and between MD and ACC. Coupled stimulations showed that some MD cells could serve as a relay for a pathway from VTA to cortex, others for a reciprocal pathway from PCx to VTA, and still others, for a pathway from PCx to ACC. These findings are compared to previous--mostly anatomical--data obtained in other species, mainly rat. Their functional meaning is also discussed, in the light of previous results on the roles of MD, VTA and ACC in the control of immobility during focused attentive behaviour in cat.

Animals↗

PubMed1987

Anatomical localization of cortical beta rhythms in cat.

Beta electrocorticographic rhythms (40 Hz) develop during motionless focused attention in two distinct cortical foci in cats. A cytoarchitectonic study was performed to determine the precise location of these foci. Electrode tips recording beta rhythms were found: (i) in motor areas 4 gamma and 6a beta, in a band extending from the postcruciate cortex to the walls of the presylvian sulcus, crossing the frontal pole (anterior beta focus); (ii) in the posterior parietal associative area 5a, along the divisions of the ansate sulcus, extending to the mesial aspect of the hemispheres (posterior beta focus). The two foci are separated by areas 3, 2 and 1, where beta rhythms were never recorded. The fact that both these areas, containing giant pyramidal cells, develop a specific type of activity during immobility may have a functional meaning: area 5 may be involved in the cat as it is in the monkey in the control of motor behaviour.

Animals↗

PubMed1986

Compulsive attentive behavior after lesion of the ventral striatum in the cat: a behavioral and electrophysiological study.

Bilateral lesions of the nucleus accumbens in cat elicited the following changes: preservation in tests requiring focused attention, with difficulty to shift to other targets; paucity of movements, animals displaying moderate hypokinesia and loss of reaction to changes in the environment. These symptoms were accompanied by a significant increase in the amount of beta rhythms, an activity that has been shown to be concomitant with the development of focused attentive behavior. The observed behavioral and electrocortical modifications are opposite those that have been previously obtained in the same species after lesions of the ventral tegmental area.

Animals↗