[Changes in muscarinic cholinergic receptors and cholinergic neurons in experimental hydrocephalic rat brain]

Recently, the relationship between neurological disorders and neurotransmitters has received much attention. Many studies have been reported about the changes of neurotransmitters and their metabolites in cerebrospinal fluid (CSF) in hydrocephalus, and it is presumed that neurotransmitters may play a role in the regulation of CSF dynamics. We injected kaolinum suspension into the cisterna magna of rats and created experimental hydrocephalus. Here we define the acute hydrocephalic stage to be the seventh day after injection and the chronic to be the twenty-first day after injection. We made studies about the changes of muscarinic cholinergic receptors in experimental hydrocephalic rat brains using binding assay, macroautoradiography, and microautoradiography with 3H-quinuclidinyl benzilate (QNB), which has a high and specific affinity for muscarinic receptors. We also studied the changes of cholinergic neurons in experimental hydrocephalic rat brains by immunohistochemical methods with anti-choline acetyltransferase (CAT), the antibody for the synthetic enzyme of acetylcholine which is thought to exist only in cholinergic neurons. Muscarinic cholinergic receptors were increased in acute hydrocephalus, and tended to normalize in chronic hydrocephalus but no change was observed in its distribution. There seemed to be no difference in the number of CAT positive cells between normal and hydrocephalic rat brains, but in hydrocephalic rat brain, CAT positive cells were compressed by the dilated ventricles, and they might have fallen into hypofunction. It is thought that muscarinic receptors were increased by some mechanism like denervation hypersensitivity because of the reduction of ACh production or release. Recent advancement of PET or SPECT has made it possible to investigate the changes of neurotransmitter receptors in human brain. Such biochemical examination may offer some information to assess the functional state of hydrocephalus and to find a new approach to its treatment.