Neuroscience
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The elderly have comparatively worse cognitive impairments from traumatic brain injury (TBI) relative to younger adults, but the molecular mechanisms that underlie this exacerbation of cognitive deficits are unknown. Experimental models of TBI have demonstrated that the cyclic AMP-protein kinase A (cAMP-PKA) signaling pathway is downregulated after brain trauma. Since the cAMP-PKA signaling pathway is a key mediator of long-term memory formation, we investigated whether the TBI-induced decrease in cAMP levels is exacerbated in aged animals. ⋯ Rolipram rescued the LTP deficits after mild TBI for young adult animals and caused a partial recovery for aged animals. However, rolipram did not rescue LTP deficits after moderate TBI in either young adult or aged animals. These results indicate that the exacerbation of cognitive impairments in aged animals with TBI may be due to decreased cAMP levels and deficits in hippocampal LTP.
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Neurons within the superficial dorsal horn (SDH) of the rodent spinal cord exhibit distinct firing properties during early life. While this may reflect a unique combination of voltage-gated Na(+) (Na(v)) and voltage-independent (i.e. "leak'') K(+) channels which strongly influence neuronal excitability across the CNS, surprisingly little is known about which genes encoding for Na(v) and leak K(+) channels are expressed within developing spinal pain circuits. The goal of the present study was therefore to characterize the transcriptional expression of these channels within the rat SDH at postnatal days (P) 3, 10, 21 or adulthood using quantitative real-time polymerase chain reaction. ⋯ In addition, a developmental shift occurred within the TREK subfamily due to decreased TREK-2 (KCNK10) mRNA within the mature SDH. Meanwhile, G-protein-coupled inward rectifying K(+) channels (K(ir)3.1 and K(ir)3.2) were expressed in the SDH at mature levels from birth. Overall, the results suggest that the transcription of ion channel genes occurs in a highly age-dependent manner within the SDH, raising the possibility that manipulating the expression or function of ion channels which are preferentially expressed within immature nociceptive networks could yield novel approaches to relieving pain in infants and children.
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In adult mammals, newborn neural precursor cells (NPCs) derived from either the subventricular zone (SVZ) or the subgranular zone (SGZ) migrate into the olfactory bulb and the dentate gyrus (DG), respectively, where some of them mature into excitatory and inhibitory neurons. There is increasing evidence that this neurogenesis process is important for some types of learning and synaptic plasticity and vice versa. Survivin, a member of the inhibitor-of-apoptosis protein (IAP) family, has been suggested to have a central role in the regulation of neurogenesis. ⋯ Here we examined adult Survivin(Camcre) mice with a conditional deletion of the survivin gene in embryonic neurogenic regions. Although the deletion of survivin had no effect on basic excitability in DG and CA1-region, there was a marked impairment of long-term potentiation (LTP) in these areas. Our data support a function of survivin in hippocampal synaptic plasticity and learning and underline the importance of adult brain neurogenesis for proper operation of the hippocampal tri-synaptic circuit and the physiological functions that depend on it.
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Adderall is widely prescribed for attention deficit hyperactivity disorder (ADHD) though long term neurological effects of the main ingredient d-amphetamine are not well understood. The purpose of this study was to examine effects of clinically prescribed doses of d-amphetamine and one abuse dose administered from childhood to adulthood on adult hippocampal neurogenesis and activation of the granule layer of the dentate gyrus. Beginning in early adolescence (age 28 days) to adulthood (age 71), male C57BL/6J mice were administered twice daily i.p. injections of vehicle, 0.25, 0.5 or 2mg/kg d-amphetamine. ⋯ Results suggest both therapeutic and abuse doses of d-amphetamine increase the number of new neurons in the hippocampus when administered from adolescence to adulthood by increasing survival and differentiation of cells into neurons not by increasing progenitor cell proliferation. Mechanisms for amphetamine-induced neurogenesis are unknown but appear activity independent. Results suggest part of the beneficial effects of therapeutic doses of d-amphetamine for ADHD could be via increased hippocampal neurogenesis.
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Fibronectin type III domain-containing 5 protein (Fndc5) or peroxisomal protein, is a type I membrane protein that has 209 amino acid residues. Previous studies by our group have shown an increase in its expression after retinoic acid treatment of mouse embryonic stem cells (mESCs) during the process of neural differentiation, leading us to conclude that it might be involved in neurogenesis. In the present study, we have constructed an inducible short hairpin RNA (shRNA) vector that is expressed under induction by doxycycline. ⋯ Fndc5 knockdown during both stages significantly affected both neuronal and astrocytes maturation. We have concluded that Fndc5 expression is required for the appropriate neural differentiation of mESCs. These data confirm the importance of Fndc5 in the generation and development of the nervous system.