Neuroscience
-
Recent experimental and clinical studies suggest that estrogen may be an important factor influencing neuronal function during normal and pathological aging. Using different behavioral paradigms in rodents, estrogen replacement was shown to enhance learning and memory as well as attenuate learning deficits associated with cholinergic impairment. The goal of this study was to determine whether cognitive sensitivity to estrogen manipulations (short-term ovariectomy and chronic estrogen replacement) is affected by aging. ⋯ These data indicate that aging processes may substantially modulate the mechanisms of estrogen action. A "time window" during which hormone replacement must be initiated in order to be effective could be determined in terms of the stages of reproductive senescence. This study is the first to clearly demonstrate that the cognitive effects of estrogen replacement are still preserved during the initial stages of reproductive aging (irregular cyclicity) and dramatically limited as aging progresses (cessation of proestrus).
-
Intracellular recordings were made from neurones in the thalamic reticular nucleus (TRN) and ventro-basal (VB) thalamus in slices of rat midbrain in vitro. Electrical stimulation of the medial lemniscus or TRN resulted in the generation of complex synaptic potentials containing disynaptic inhibitory post-synaptic potentials (IPSPs) in VB thalamocortical neurones. Analysis of the excitatory synaptic responses in TRN neurones indicates they can produce burst output response irrespective of the level of sub-threshold membrane potential. ⋯ This is consistent with the location of these receptor types on the presynaptic terminals of TRN axons in the VB thalamus. This raises the possibility that, during periods of intense excitatory activity, glutamate release could influence the release of GABA from TRN axon terminals in the thalamus. In addition, as NAAG is located in the axons and terminals arising from the TRN, there is the possibility that this dipeptide is also released by these terminals to control the release of GABA during periods of high activity in the TRN.
-
Comparative Study
Expression pattern of the stem cell leukaemia gene in the CNS of the embryonic and adult mouse.
The basic helix-loop-helix (bHLH) transcription factor stem cell leukaemia (SCL) is a 'master regulator' of haematopoiesis, where SCL is pivotal in cell fate determination and differentiation. SCL has also been detected in CNS, where other members of the bHLH-family have been shown to be indispensable for neuronal development; however, no detailed expression pattern of SCL has so far been described. We have generated a map of SCL expression in the embryonic and adult mouse brain based on histochemical analysis of LacZ reporter gene expression in sequential sections of brain tissue derived from SCL-LacZ knockin mice. ⋯ LacZ staining was also evident in parts of the intermediate and marginal zone of the aqueduct and ventricular zone of the fourth ventricle at E12.5 and E14. These cells may represent progenitor stages of differentiating neural cells. Given the presence of SCL in both the developing brain and in post-mitotic neurons, it seems likely that the function of SCL in neuronal differentiation may differ from its function in maintaining the differentiated state of the mature neuron.
-
Focal traumatic injury to the cerebral cortex is associated with early activation of the neuronal isoform of nitric oxide synthase (nNOS), where high concentrations of nitric oxide-derived free radicals elicit extensive DNA damage. Subsequent activation of the nuclear repair enzyme poly(ADP-ribose) polymerase (PARP) causes a severe energy deficit leading to the ultimate demise of affected neurons. Little is known about the temporal relationship of nNOS and PARP activation and the neuroprotective efficacy of their selective blockade in traumatic brain injury. ⋯ In contrast, i.p. AB treatment remained largely ineffective. In conclusion, our data indicate early activation of PARP after cold lesion that is, at least in part, related to nNOS induction and supports the relevance of nNOS and/or PARP inhibition to therapeutic approaches of traumatic brain injury.
-
The genioglossus muscle is involved in the maintenance of an open airway for effective breathing. Inhibitory neurotransmitters may be responsible for the major suppression of hypoglossal motor output to genioglossus muscle that occurs in certain behaviours such as rapid-eye-movement sleep. There is evidence for GABA(A) receptor-mediated inhibition of hypoglossal motoneurons in vitro. ⋯ Antagonism of GABA(A) receptors increased genioglossus activity (P<0.001). These results show that GABA(A) receptor stimulation at the hypoglossal motor nucleus suppresses both genioglossus muscle tone and activity in the presence of reflex stimulation produced by hypercapnia. Recruitment of such mechanisms may contribute to the major suppression of genioglossus activity observed with and without CO(2) stimulation in behaviours such as rapid-eye-movement sleep.