Neuroscience
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The spinal Neuropeptide Y (NPY) system is a potential target for development of new pain therapeutics. NPY and two of its receptors (Y1 and Y2) are found in the superficial dorsal horn of the spinal cord, a key area of nociceptive gating and modulation. ⋯ In the present study, we sought to determine the role of dorsal horn Y1R-expressing neurons in pain by destroying them with NPY-sap and testing the rats on three operant tasks. Lumbar intrathecal NPY-sap (1) reduced Complete Freund's Adjuvant (CFA)-induced hyper-reflexia on the 10°C cold plate, (2) reduced cold aversion on the thermal preference and escape tasks, (3) was analgesic to noxious heat on the escape task, (4) reduced the CFA-induced allodynia to cold temperatures experienced on the thermal preference, feeding interference, and escape tasks, and (5) did not inhibit or interfere with morphine analgesia.
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Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. ⋯ Immunocytochemistry was performed on differentiated cultures to detect mature neurons. To explore the expression of certain important transcriptional factors involved on asymmetric cell division and commitment, RT-PCR and qRT-PCR were performed. Results indicate that HA is required during cell proliferation in order to increase neuron differentiation and suggest that this amine increases neuron commitment during the proliferative phase probably by rising prospero1 and neurogenin1 expression.
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Akt has been demonstrated as a survival kinase in brain after hypoxia-ischemia (HI). Previous studies have shown that glycogen synthase kinase-3β (GSK-3β)/collapsin response mediator protein 2 (CRMP-2) signaling pathway could be regulated by Akt for axonal-dendritic polarity. CRMP-2 is associated also with microtubule-mediated trafficking. ⋯ Furthermore, Akt inhibition significantly decreased the phosphorylation of GSK-3β and dephosphorylation of CRMP-2. Moreover, the down-regulation of dephosphorylated CRMP-2 was associated with increased axonal injury (increased APP expression and axonal loss). Our findings suggest that the Akt/GSK-3β/CRMP-2 pathway mediates axonal injury in neonatal rat brain after HI.
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The cortical cholinergic innervation, which is important for memory and cognition, has been implicated in schizophrenia. To experimentally analyze such a possible role of the cholinergic system, we have used the dissociative drug phencyclidine (PCP), known to produce schizophrenia-like psychosis in humans, to model aspects of schizophrenia in rats. We previously showed that induced cortical cholinergic hypofunction leads to enhanced PCP-induced locomotor activity and attenuated social interaction. ⋯ Specific unilateral lesioning of the uncrossed cholinergic projections to the cortical mantle by 192-IgG-saporin immunotoxin delivery to nc basalis (NBM) caused a striking ipsilateral decrease of the PCP-induced cortical c-fos mRNA induction, restricted to areas which had become effectively denervated. Because PCP at low doses is unlikely to directly influence cortical neurons, we suggest that it acts by activation of the cholinergic input, which in turn leads to cortical c-fos mRNA increases. Our results are compatible with a role for the cholinergic system in symptoms of schizophrenia, by showing that the basalo-cortical cholinergic projections are needed in order for PCP to have full activating effects on cortical neurons.