Françoise Eclancher

Behavioural and glial changes in old rats following environmental enrichment.

The effects of enriched environment on short-term memory for event durations and on astrocytes (cell density, cell area and % of GFAP immunoreactivity) in hippocampus (Hi), frontal cortex (FC) and corpus callosum (CC) were analysed in old rats housed from weaning to the end of behavioural testing (23 months) either in standard (SC) or in enriched (EC) conditions and in young adults (5 months) all housed in SC. Old SC and EC and young SC rats trained (for 2 months) or not, in a Symbolic Delayed Matching to Sample Task, had to discriminate and remember two (2- and 10-s) signals after short retention intervals. Results confirm the aging-related acquisition and memory deficit. EC reduced the slowness of acquisition, reversed the short-term memory deficit and promoted the retention of the short signal (choose short effect). Old SC naive rats had many hypertrophied astrocytes with long processes in Hi and CC while old EC rats had decreased astrocytes number and size. The behavioural testing resulted in young adult SC rats in Hi and CC, in increased astrocytes number, size and GFAP% and in their decrease in old SC rats. EC and testing have additive effects (very low astrocytes number, size and GFAP%) to compensate for the aging-induced gliosis, mostly in Hi.

Basic fibroblast growth factor (bFGF) injection activates the glial reaction in the injured adult rat brain

Reactive gliosis is a reaction of glial cells to trauma which is characterized by a phenotypic modification of astrocytes, as well as by a proliferation and a migration of some of these cells to form a glial scar. This scar is currently considered as a physical impediment to neuronal regrowth but it may also be involved in wound healing since the astrocytes beside microglia play a phagocytic role in the clearance of post-traumatic debris. Growth factors are released in the area of the injury and at least some of them could be involved in gliosis. In order to test directly this possibility, we have injected one of them, the basic fibroblast growth factor (bFGF), into several brain areas (cortex, striatum, hippocampus or corpus callosum) of adult 2-month-old rats in the absence of lesion. A glial reaction was observed after 3 days and was maximum after 7 days. It was characterized by an increase in astrocyte proliferation and in glial fibrillary acidic protein (GFAP) expression, resulting in a higher number of GFAP-positive cells per surface unit, and by an increase in the size and branching of the astroglial processes. The GFAP mRNA levels were also strongly increased following the bFGF injection. These effects resemble the reactive gliosis observed after lesion and suggest that bFGF is actually involved in the triggering of glial reactions which follow brain injury. In further experiments, bFGF was injected in the site of electrolytic lesions made in the same various parts of the brain. These injections did not increase significantly the normal reactive gliosis induced by the lesion alone, but it accelerated some of the effects. It also resulted in a higher labeling index and GFAP mRNA levels were strongly enhanced after a 3-day-post-operative delay. This last observation strengthens the idea that one of the main factors driving the astrogliosis is the bFGF normally released in and around the site of the lesion.

Primary Cultures of Astrocytes from Different Brain Areas of Newborn Rats and Effects of Basic Fibroblast Growth Factor

The effects of basic fibroblast growth factor (bFGF) on the morphology and the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) in cultured astrocytes prepared from various areas of newborn rat brain was studied. The brain was dissected in two ways, either the telencephalon (area A) and the diencephalon (area B) were dissected out of the brain (without olfactory bulbs, mesencephalon and cerebellum) or the brain was cut transversely into 3 parts (areas 1, 2 and 3). Area 1 (the anterior part) included the frontal cortex, the olfactory nuclei, the neostriatum, the accumbens nucleus and the septum; area 2 (the medial part) included the cortex, hippocampus, amygdale, thalamus and hypothalamus, and area 3 (the posterior part) included the occipital cortex, the posterior part of hippocampus and thalamus and the mamillary bodies. Essentially two different morphological aspects were observed. Most cells from areas A, 1 and 3, were flat, large, presented an irregular shape and were loosely arranged; cells from areas B and 2 were essentially polygonal in shape and closely apposed to each other. The various control cultures showed nearly the same immunostaining pattern for GFAP, but different patterns for GS. Most astroglial cells responded to bFGF and became fibrous. The GFAP immunoreaction was intense and localized in the cell bodies and processes of most cells from area A, but essentially in the processes for cells from areas 1 and 2. The immunoreactivity was weaker in cells from areas B and 3. GS-positive cells, heavily and weakly stained, were found in all treated cultures, and very strongly stained cells were located in certain zones of cultures from area A. But GS-negative cells were also seen in these treated cultures as well as in control cultures. Measurements of GS activities revealed no differences. These results indicate that astrocytes from different regions of the brain in primary culture show differences in their responsiveness to bFGF. The astroglial cells from the cerebral cortex and from the thalamus seem to present the highest and the lowest response to bFGF, respectively.

Timed hypocaloric feeding and melatonin synchronize the suprachiasmatic clockwork in rats, but with opposite timing of behavioral output

Temporal organization of the molecular clockwork and behavioral output were investigated in nocturnal rats housed in constant darkness and synchronized to nonphotic cues (daily normocaloric or hypocaloric feeding and melatonin infusion) or light (light–dark cycle and daily 1‐h light exposure). Clock gene (Per1, Per2 and Bmal1) and clock‐controlled gene (Vasopressin) expression in the suprachiasmatic nuclei was assessed over 24 h. Light and exogenous melatonin synchronized the molecular clock, signaling, respectively, ‘daytime’ and ‘nighttime’, without affecting temporal organization of behavioral output (rest/activity rhythm). By contrast, synchronization to hypocaloric feeding led to a striking temporal change between gene expression in the suprachiasmatic clock and waveform of locomotor activity rhythm, rats then becoming active during the subjective day (diurnal‐like temporal organization). When the time of feeding coincided with activity offset, normocaloric feeding also synchronized the locomotor activity rhythm with no apparent switch in temporal organization. Peak of Per2 expression in the piriform cortex occurred between the beginning and the middle of the activity/feeding period, depending on the synchronizer. These data demonstrate that even though the suprachiasmatic clockwork can be synchronized to nonphotic cues, hypocaloric feeding likely acts downstream from clock gene oscillations in the suprachiasmatic nuclei to yield a stable yet opposite organization of the rest/activity cycle.

Effects of infant and adult amygdaloid lesions upon acquisition of two-way active avoidance by the adult rat: influence of rearing conditions.

Abstract When performed in the adult rat, bilateral and complete amygdalectomy resulted in a clear deficit in the acquisition of a 2-way active avoidance in a shuttle-box. When performed in the 7 day old rat pup, the same complete lesion resulted in no disruption of acquisition of the 2-way AA task by the rats when adult, irrespective of the environmental conditions in which they were reared from weaning. However, isolation-reared rats showed shorter response latencies than did group-reared rats. When the amygdaloid lesion was restricted to the centromedial area of the amygdala, operations carried out at 7 days resulted in a reliable impairment of the 2-way active avoidance in the initial phase of the acquisition, but only when the rats had been group-reared from weaning. The same lesion resulted in a reliable improvement in acquisition when the rats had been reared in isolation. In short, the degree of recovery of function with respect to 2-way AA acquisition following a bilateral amygdaloid lesion depends on the age at which the lesion is carried out (at infant or adult age), on the extent of the lesion (complete or restricted to the CM area) and on the rearing conditions (in groups or in isolation).

Effects of early amygdaloid lesions on the development of reactivity in the rat

Abstract When carried out in 7–8 day old rats housed in grouped condition following weaning, bilateral amygdaloid lesions provoke a lasting hyperreactivity in terms of increased locomotor activity and higher rearing scores in the openfield. The lesion-induced hyperreactivity which is clearly apparent at 40 days and which persists till adult age, is less marked if the weaned rats are housed in isolation. When carried out at the age of 25 days, amygdaloid lesions enhance even more the rats responsiveness to a novel environment. Early amygdaloid lesions provoke a marked increase in the proportion of rats that display mouse-killing behavior when adult, a behavioral effect that can be linked up with their hyperreactivity. On the contrary, bilateral amygdaloid lesions carried out in adult rats (at 3 months of age) do not change their responsiveness in the open-field, and only a small proportion of the lesioned rats (35 percent) spontaneously display mouse-killing behavior. It is concluded from the data obtained that the amygdala is involved in two closely related processes which play an important role in the ontogenetic development of the rats reactivity and social responses. On the one hand, the amygdala takes an essential part in the setting up of a stable inhibition of aggressive responses on the basis of social interactions; on the other hand, it is involved in mechanisms which progressively lessen in a more general way the organisms reactivity to its environment.

Influence of rearing conditions on the acquisition of the two-way active avoidance responses by rats septalectomized at an early age

When performed in the adult 3-month old rat, septal lesions facilitated the acquisition of a two-way active avoidance (AA) task as compared to animals sham-operated at the same age. When performed in the 7-day-old rat pup, the same lesion also clearly facilitated the 2-way AA acquisition by the rats when adult and, more especially so, when the rats were isolation-reared from weaning. The performances of these early-septal rats reared in isolation did not differ from those of rats septalectomized at adult age, while the performances of the early-septal rats that had been group-reared from weaning proved to be lower than that of adult-operated rats, with regard to both number of shocks avoided and mean response latencies in the initial phase of acquisition. The improvement of the 2-way AA acquisition following septal lesion may result from an increased responsiveness to aversive stimulation and this responsiveness may be enhanced if the early-septal rats are reared in isolation from weaning.

Distribution in ocular structures and optic pathways of immunocompetent and glial cells in an experimental allergic encephalomyelitis (EAE) relapsing model

Relapsing experimental allergic encephalomyelitis (EAE) was induced in DA rats and the ocular pathologic events were examined at the various phases of the illness. About 80% of EAE rats presented anterior uveitis (AU), even after complete EAE recovery. We studied the phenotype and localization of immunocompetent cells, the major histocompatibility complex (MHC) class I and II antigen expression, as well as the chemokine monocyte chemoattractant protein‐1 (MCP‐1) appearance. In control animals, there were many glial fibrillary acidic protein (GFAP)+ cells and OX42+ cells in the ciliary body, retina, optic nerve and chiasma. Except in retina, we observed constitutive MHC class I and II expression. During the EAE acute phase, there was up‐regulation of MHC class II and GFAP antigens in iris, ciliary body, limbus, and optic pathways. MHC class I and ED2 antigens were expressed in meninges and in the prechiasmatic cisterna, by cells which could have a role in immune surveillance. MCP‐1 mRNA was highly expressed in optic pathways during the acute phase and the protein was expressed by astrocytes, macrophages, and lymphocytes. During the relapsing phase, MCP‐1 was weakly expressed to disappear almost completely during the final recovery phase. The expression of MHC class II on astrocytes was increased during the relapsing and final recovery phase in which the inflammatory lesions persisted. These findings suggest that ocular areas and optic pathways, mainly optic chiasma, are important targets in the relapsing EAE. J. Neurosci. Res. 63:525–535, 2001.

Ontogeny of Acquisition And Retention of Two-Way Active Avoidance in the Rat: Effects of Early Septal Damage

It has been reported that young rats can perform similarly to adults in an active avoidance task (Kirby, 1963; Campbell, 1967; Denenberg and Kline, 1958; Feigley and Spear, 1970; Riccio et al., 1968). However, other authors have reported that active avoidance performances appear to improve as a function of age. Egger and Livesey (1972) found that 24 day-old rats required more training to learn the active avoidance task than did 100 day-old rats, and Izquierdo et al. (1975) observed that 20–21 day-old rats made fewer conditioned avoidance responses than did 55–70 day-old adult rats in an acquisition session and showed no retention of these responses.

Gliosis Growth Factors in the Adult and Aging Rat Brain

Gliosis is a response of glial cells (consisting usually in hypertrophy, migration, proliferation, and phenotypic changes) to various types of neural tissue perturbations. This glial response occurs naturally in aged animals. Notwithstanding the nature of the trauma, the glial response is more or less stereotypical. A reproducible succession of cellular and molecular events develops, coordinated by intercellular signaling in which growth factors and extracellular matrix seem to play a major role. Gliosis can occur in any part of the central nervous system (CNS). Prominent responses that follow brain trauma include the activation of microglia, recruitment of blood-derived macrophages, and astroglial reactivity. Occasionally, depending on the zone of gliosis, other cell types can be activated like ependymal cells, endothelial cells, meningeal cells, and Schwann cells. The main aspect of localized gliosis is the elaboration of a glial scar which forms a physical and biochemical barrier preventing axonal regeneration and remyelination. In addition to this physical repair, many data suggest that gliosis contributes to nerve survival and to immunological protection.