Evidence for a neurotrophic role of noradrenaline neurons in the postnatal development of rat cerebral cortex

Summary

The effects of neonatal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA; 1–4 doses of 100 mg/kg body weight s.c.) on the postnatal development of pyramidal neurons in several cortical regions of the rat was studied using a Golgi-Cox neuronal impregnation technique. Rats were sacrificed in the adult stage (eight weeks) and the following regions were studied: anterior frontal cortex, posterior frontal cortex (including motor cortex), anterior parietal cortex (including sensory cortex), posterior parieto-occipital cortex and cingulate cortex. Significant alterations were seen in animals which received four doses of 6-OHDA. These alterations can be summarized as follows: (1) a decreased length and branching of basolateral dendrites of pyramidal cells, with loss of dendritic spines, which were found in both the internal pyrimidal layer (layer V) and the external pyramidal layer (layer III), most abundantly in the frontal cortex and cingulate cortex; (2) an increased number of pyramidal cells of layer V with premature apical dendritic termination in layer III rather than the usual termination in layers I and II. This was most abundant in the cingulate cortex; (3) occasional disorientation of pyramidal cell apical dendrites away from the normal vertical plane by 15 or more degrees, seen in frontal, parietal and cingulate cortex; (4) an increased number of pyramidal cells with rounded somatic contours, found in frontal, anterior parietal and cingulate cortex. These phenomena were occasionally seen in normal cortex, but were significantly increased in their occurrence after four doses of 6-OHDA. Such alterations were not significant in rats treated with one or three doses of 6-OHDA. The extent and severity of morphological alterations correlate with reductions in endogenous noradrenaline (NA) in cerebral cortex, which was found to average 50% of control levels after one dose of 6-OHDA, an 80% reduction after three doses, and a 97–98% reduction after four doses, suggesting that the NA denervation must be almost complete to result in readily detectable significant morphological changes in the development of cortical pyramidal cells. No consistent changes in endogenous dopamine (DA) levels were observed, except for an increase in the cingulate cortex. The anatomical alterations in pyramidal cells described in the present study suggest that NA neurons which project into the cerebral cortex have a neurotrophic role in the postnatal development of cortex.