| Since the central nervous system lacks of regenerative ability in mature mammal, traumatic brain injury(TBI) which is frequently encountered in clinic may leads to severe sensory, motor and cognitive dysfunction. It is widely regarded that the functional recovery of central nervous system following brain injury primarily depends on compensation of functionally associated area nearby or remote. It may also depends on the unmasking or reorganization of some existent potential network. The metabolism and the functional alteration of various neurotransmitters in the brain play important roles in these mechanisms. 5-hydroxytryptamine (5-HT) is an excitatory neurotransmitter in mammalian central nervous system. It is involved in numerous physiological processes including food intake, emotion, sleep, learning and memory. 5-HT6 receptor is one of the subtypes of 5-HT receptor families , which has been proven to be almost exclusively localized within mammal central nervous system , particularly in striatum, hippocampus and cerebral cortex .There are convincing evidences that 5-HT6 receptor fulfills a significant role in learning and memory via regulating the release of neurotransmitters such as acetylcholine, glutamate andγ-aminobutyric acid(GABA). Furthermore, the 5-HT6 receptor antagonists has been proved to improve the intelligent in experimental dementia rodent animal.ObjectiveWe observe the temporal time-course of 5-HT6 receptor expression in the mice experimental traumatic brain injury so as to investigate the role of 5-HT6 receptor in the recovery of cortex function. MethodsThe weigh-drop brain injury model was employed to cause traumatic brain injury (TBI) in mice. Both the 5-HT6 receptor mRNA expression and the level and distribution of 5-HT6 receptors in posttraumatic mouse brain at the 1st day, 7th day, 14th day and the 28th day respectively were also detected by techniques of fluorescent quantitative PCR and immunohistrochemistry .ResultsThe expression of 5-HT6 receptor mRNA in post-traumatic mice1,The 5-HT6 receptor mRNA relative value(5-HT6R copies/18SrRNA copies) in lesioned hemisphere of traumatic brain injury groups(TBI) was 1.48±0.76, 1.35±0.72 at 1d, 7d respectively ,which was increased significantly compared with 0.78±0.30, 0.66±0.16 of psudo-operation groups (p<0.05) . However, no significant difference was found between the traumatic brain injury groups at 14d and 28d respectively (p>0.05) .The 5-HT6 receptor mRNA relative value in contraleteral cortex of psudo-operation groups (PS) was 1.30±0.40, 1.44±0.52 at 1d and 7d ,which was increased significantly compared with 0.89±0.20, 0.75±0.22 of psudo-operation groups (PS) (p<0.05) . However, no significant difference was found between traumatic brain injury groups at 14d and 28d respectively) compared with the psudo-operation groups (p>0.05) .2,The expression and distribution of 5-HT6 receptor in post-traumatic mice 5-HT6R is condense expressed on the membrane, cytoplasm and axon of neurons in hippocampus, striatum as well as cerebral cortex symmetrically. It particularly in the layer 3 and layer 4 neuron on cerebral cortex and appeared as positive dark brown signal on the cell membrane, cytoplasm or axons in immunohistochemistry stain..Immunohistochemical staining showed that the expression of 5-HT6 receptor in the neighbouring regions of the TBI and the controleteral cortex in post-traumatic mice were obviously higher than the control groups. The immunohistochemical gray scale of 5-HT6 receptor in lesioned hemisphere of TBI was 0.74±0.25 at 1st day, which has no significance compared with 0.60±0.17 of psudo-operation groups (PS) (p1d>0.05). However, the gray scales on the ipsileteral of brain injury in TBI at 7d, 14d and 28d group were 1.08±0.34, 0.73±0.11 and 0.67±0.07 respectively, they were significantly higher than those in the psudo-operation group(0.50±0.10, 0.45±0.05 and 0.50±0.04)( p7d,p14d<0.01,p28d<0.05) .The immunohistochemical gray scales of 5-HT6 receptor in contraleteral hemispheres of traumatic brain injury was 0.61±0.05, 0.70±0.16 and 0.66±0.05 at 1d, 7d and 14d group respectively, which was notable increased comparing with 0.46±0.07, 0.52±0.05 and 0.52±0.06 in psudo-operation groups (p<0.05) . The grey scales had no significant difference between the traumatic brain injury groups(TBI) ( 0.50±0.10) and the psudo-operation groups (PS) ( 0.53±0.07) at the 28th day after trauma(p>0.05) .Conclusion1. The expression level of 5-HT6R mRNA in the neurons of lesioned hemisphere in post-traumatic mice was elevated at the first day, and maintained at higher level within 7 days. It returned to the normal level at 14d. The expression of 5-HT6R began increasing and rapidly reached the peak at the 7d, then maintained at the higher level over 28 days.2. The expression level of 5-HT6R mRNA in the neurons of contraleteral of TBI were increased compensatively at the 1st day, then up to the peak at the 7th days and maintained at high level within 14 days,eventually it returned to normal level at the 28th day.3. The increasing expression of 5-HT6R mRNA and 5-HT6R in both ipsileteral and contraleteral cortex of mouse traumatic brain injury may be related to the recovery of motor activity and cognition impairment after TBI. |
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