Detailed Differentiation of Calbindin D-28k-Immunoreactive Cells in the Dentate Gyrus in C57BL/6 Mice at Early Postnatal Stages

The hippocampus makes new memories and is involved in mental cognition, and the hippocampal dentate gyrus (DG) is critical because neurogenesis, which occurs throughout life, occurs in the DG. We observed the differentiation of neuroblasts into mature neurons (granule cells) in the DG of C57BL/6 mice at various early postnatal (P) ages: P1, P7, P14, and P21 using doublecortin (DCX) immunohistochemistry (IHC) for neuroblasts and calbindin D-28k (CB) IHC for granule cells. DCX-positive cells decreased in the DG with age; however, CB+ cells increased over time. At P1, DCX and CB double-labeled (DCX+CB+) cells were scattered throughout the DG. At P7, DCX+CB+ cells (about 92% of CB+ cells) were seen only in the granule cell layer (GCL) of the dorsal blade. At P14, DCX+CB+ cells (about 66% of CB+ cells) were found in the lower half of the GCL of both blades. In contrast, at P21, about 18% of CB+ cells were DCX+CB+ cells, and they were mainly located only in the subgranular zone of the DG. These results suggest that the developmental pattern of DCX+CB+ cells changes with time in the early postnatal stages

Conditional ablation and recovery of forebrain neurogenesis in the mouse

Forebrain neurogenesis persists throughout life in the rodent subventricular zone (SVZ) and hippocampal dentate gyrus (DG). Several strategies have been employed to eliminate adult neurogenesis and thereby determine whether depleting adult-born neurons disrupts specific brain functions, but some approaches do not specifically target neural progenitors. We have developed a transgenic mouse line to reversibly ablate adult neural stem cells and suppress neurogenesis. The nestin-tk mouse expresses herpes simplex virus thymidine kinase (tk) under the control of the nestin 2nd intronic enhancer, which drives expression in neural progenitors. Administration of ganciclovir (GCV) kills actively dividing cells expressing this transgene. We found that peripheral GCV administration suppressed SVZ-olfactory bulb and DG neurogenesis within 2 weeks but caused systemic toxicity. Intracerebroventricular GCV infusion for 28 days nearly completely depleted proliferating cells and immature neurons in both the SVZ and DG without systemic toxicity. Reversibility of the effects after prolonged GCV infusion was slow and partial. Neurogenesis did not recover 2 weeks after cessation of GCV administration, but showed limited recovery 6 weeks after GCV that differed between the SVZ and DG. Suppression of neurogenesis did not inhibit antidepressant responsiveness of mice in the tail suspension test. These findings indicate that SVZ and DG neural stem cells differ in their capacity for repopulation, and that adult-born neurons are not required for antidepressant responses in a common behavioral test of antidepressant efficacy. The nestin-tk mouse should be useful for studying how reversible depletion of adult neurogenesis influences neurophysiology, other behaviors, and neural progenitor dynamics. J. Comp. Neurol. 514:567–582, 2009. © 2009 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62155/1/22052_ftp.pd

Izloženost štakora niskim razinama olova tijekom fetalnog i ranoga postnatalnog razvoja šteti učenju pasivnim izbjegavanjem kazne kasnije u odrasloj dobi

This follow-up study investigated the effects of low-level lead exposure during prenatal and early postnatal period on learning and memory in rats immediately after exposure has ceased at weaning and later in their adulthood. Male Wistar-derived rats were exposed to lead (as 0.2 % lead acetate solution) through their mothers during pregnancy and lactation until they were weaned. Mothers of control rats were given tap water during pregnancy and lactation. All pups were weaned on tap water at 21 days of age and were followed up until 120 days old. Low-level lead exposure did not affect their body weight at any time during the experiment. Blood lead in the exposed rats was significantly higher on postnatal day 22 and dropped to control values by day 120. Passive avoidance test showed impaired memory retention in the exposed rats on postnatal days 25 and 120. This suggests that exposure to low-lead levels during foetal and early postnatal development of brain tissue can cause memory impairment that lasts into adulthood.Cilj je ovoga prospektivnog istraživanja bio utvrditi kako izloženost niskim razinama olova tijekom gestacije i ranoga postnatalnog razvoja utječe na učenje i pamćenje u štakora odmah nakon prestanka izloženosti (odbijanjem od sise) te kasnije u odrasloj dobi. Mužjaci štakora izloženi su olovu u obliku 0,2 %-tne otopine olovova acetata preko majke tijekom gestacije te za cijeloga trajanja laktacije sve do odbijanja od sise. Sve to vrijeme majke kontrolnih štakora dobivale su vodu iz pipe. Svi su štakorčići odbijeni od sise 21 dan nakon okota i otada piju vodu iz pipe. Praćeni su do 120. dana života. Izloženost niskim razinama olova nije dovela do razlika u tjelesnoj težini između izloženih i kontrolnih štakorčića. Razine olova u krvi bile su značajno više u izloženih štakora 22 dana od okota, da bi do 120. dana pale na razinu u kontrolnih štakora. Test pasivnoga izbjegavanja pokazao je oštećenje pamćenja u izloženih štakora 25. i 120. dana nakon okota. To potvrđuje da izloženost niskim razinama olova tijekom fetalnoga i ranoga postnatalnog razvoja moždanog tkiva može dovesti to oštećenja u pamćenju koje traje sve do odrasle dobi

Excessive novelty-induced c-Fos expression and altered neurogenesis in the hippocampus of GluA1 knockout mice

a−Amino−3−hydroxy−5−methyl−4−isoxazolepropionic acid (AMPA) receptor GluA1 subunit−deficient (GluA1) / )) mice display noveltyinduced hyperactivity, cognitive and social defects and may model psychiatric disorders, such as schizophrenia and depression / mania. We used c−Fos expression in GluA1) / ) mice to identify brain regions responsible for novelty−induced hyperlocomotion. Exposure to a novel cage for 2 h significantly increased c−Fos expression in many brain regions in both wild−type and knockout mice. Interestingly, the clearest genotype effect was observed in the hippocampus and its main input region, the entorhinal cortex, where the novelty−induced c−Fos expression was more strongly enhanced in GluA1) / ) mice. Their novelty−induced hyperlocomotion partly depended on the activity of AMPA receptors, as it was diminished by the AMPA receptor antagonist 2,3−dioxo−6−nitro−1,2,3,4− tetrahydrobenzo[f]quinoxaline−7−sulphonamide (NBQX) and unaffected by the AMPA receptor potentiator 2,3−dihydro−1,4−benzodioxin− 6−yl−1−piperidinylmethanone (CX546). The hyperlocomotion of GluA1) / ) mice was normalised to the level of wild−type mice within 5−6 h, after which their locomotion followed normal circadian rhythm and was not affected by acute or chronic treatments with the selective serotonin reuptake inhibitor escitalopram. We propose that hippocampal dysfunction, as evidenced by the excessive c− Fos response to novelty, is the major contributor to novelty−induced hyperlocomotion in GluA1) / ) mice. Hippocampal dysfunction was also indicated by changes in proliferation and survival of adult−born dentate gyrus cells in the knockout mice. These results suggest focusing on the functions of hippocampal formation, such as novelty detection, when using the GluA1) / ) mouse line as a model for neuropsychiatric and cognitive disorder