Brain aromatase activity and plasma testosterone levels are elevated in aggressive male mice during early ontogeny

Testosterone (T) and estradiol (E(2)) are involved in intraspecific aggressive behavior. Both steroids exert their effects on behavior via the hypothalamus and the amygdala (Am) of the central nervous system (CNS). In these brain areas T is converted to E(2), by the enzyme aromatase. Both the levels of brain aromatase activity (AA) and the effects of T and E(2) on aggressive behavior in adulthood depend on steroidal organization of the CNS during ontogeny. In this study we measured plasma T and in vitro brain AA of male fetuses and neonates derived from two strains of wild house mice, which had been genetically selected for aggression, based upon attack latency. There were no differences in preoptic area (POA) AA levels between selection lines on either embryonic day (E) 17 or 18, or the day after birth (day 1). In the non-aggressive long attack latency (LAL) males the POA AA increases with age, i.e. was higher on E18 than on E17, which is correlated with brain weight (BrW). This was in contrast to aggressive short attack latency (SAL) fetuses, which only showed a slight, but not significant difference between embryonic days or, a correlation with BrW. Neonatally, the POA AA of LAL males tended to decrease in contrast to SAL males. However, SAL neonates had a higher AA in the amygdala (Am) than LAL neonates, whereas no differences exist in the anterior hypothalamus. Thus, a differential brain AA distribution exists in SAL and LAL pups. At day 1 SAL: males show higher AA in the Am than in the hypothalamus (POA + AH), whereas in the LAL strain the AA did not differ between these brain areas. In the LAL males plasma T levels decreased from E17 to day 1, whereas the SAL neonates (day 1) exhibited higher circulating T concentrations than LAL neonates. These results suggest a T-independent aromatase induction prenatally in both selection lines, whereas neonatally the higher plasma T level in the SAL line coincides with higher AA levels:in the Am. Accordingly, a differential pattern of E(2) formation exists in the brains of the two selection lines during ontogeny. The variation in circulating T and maximal brain E(2) formation around birth might result in a differential organization of adult CNS sensitivity to sex steroids and accordingly differences in aggressive behavior.</p

Long-term effects of cholinergic basal forebrain lesions on neuropeptide Y and somatostatin immunoreactivity in rat neocortex

The effect of cholinergic basal forebrain lesions on immunoreactivity to somatostatin (SOM-i) and neuropeptide-Y (NPY-i) was investigated in the rat parietal cortex, 16-18 months after multiple bilateral ibotenic acid injections in the nucleus basalis complex. As a result of the lesion, the cholinergic fiber density in the cortex decreased by 66% with a concurrent increase in SOM-i fibers by more than 50% and a 124% increase in NPY-i fiber innervation. The neuropeptidergic sprouting response on cholinergic denervation does not match the concurrent cholinergic and peptidergic decline in Alzheimer's disease and as such does not support the cholinergic lesion alone as an animal model for this neurodegenerative disorder.

Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning

In the present study, we examined changes in immunoreactivity (ir) for the gamma-isoform of protein kinase C (PKCgamma) in mouse hippocampus in relation to spatial memory processes employing the monoclonal antibody 36G9 raised against purified PKCgamma. Learning and memory were assessed by performance in a free-choice spatial pattern paradigm in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes. Adult male house mice were used, divided in four groups. Three control groups were formed: group N, naive (blank controls); group H, habituated (animals were for 5 consecutive days introduced to the hole board with all holes baited); and group PT, pseudotrained (animals were for 13 consecutive days introduced to the hole board with all holes baited). The T (trained) group was for 5 consecutive days introduced to the hole board with all holes baited (similar to the H and PT groups) followed by 8 successive days with only four holes baited in a fixed pattern. Behaviorally, following the first 5 d, the PT group crossed the hole board randomly, whereas the T group gradually learned to orientate in the hole board. The mice were killed 24 hr after the last performance. A shift in 36G9-ir appeared from the cell somata to the dendrites of hippocampal principal neurons when comparing the H and PT group, respectively. In contrast, the T group showed strong PKCgamma-ir in both cell somata and dendrites, which clearly exceeded that of the H and PT mice. In this way, 36G9-ir reveals the physiologically activated neurons involved in hole board learning. The present results, showing changes in PKCgamma-ir and redistribution of hippocampal PKCgamma induced by hole board learning, are consistent with the observation that PKC is involved in spatial memory processes

Distinct lateral septal vasopressin innervation in aggressive and non-aggressive mice

The vasopressinergic (VP) projection from the bed nucleus of the stria terminalis (BNST) to the lateral septum (LS) is sexually dimorphic and dependent of androgens at adult and neonatal age. We studied the relation between testosterone (T) and VP in male mice, which were genetically selected for their differences in aggression level. Aggressive males, characterized by a short attack latency (SAL), have a higher production capacity of T at adult age compared to males with a long attack latency (LAL). Neonatally, however, a higher T production occurs in the nonaggressive LAL males than in SAL males. In the present study we showed a more dense VP-immunoreactive (VP-ir) innervation in the LS and a higher VP-ir neuron density in the BNST of LAL males as compared to SAL males. The described differences may be the consequence of a differential neonatal androgen effect on the organization of the forebrain vasopressinergic network.

Changes in PKCγ lmmunoreactivity in Mouse Hippocampus Induced by Spatial Discrimination Learning

In the present study, we examined changes in immunoreactivity (ir) for the γ-isoform of protein kinase C (PKCγ) in mouse hippocampus in relation to spatial memory processes employing the monoclonal antibody 36G9 raised against purified PKCγ. Learning and memory were assessed by performance in a free-choice spatial pattern paradigm in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes. Adult male house mice were used, divided in four groups. Three control groups were formed: group N, naive (blank controls); group H, habituated (animals were for 5 consecutive days introduced to the hole board with all holes baited); and group PT, pseudotrained (animals were for 13 consecutive days introduced to the hole board with all holes baited). The T (trained) group was for 5 consecutive days introduced to the hole board with all holes baited (similar to the H and PT groups) followed by 6 successive days with only four holes baited in a fixed pattern. Behaviorally, following the first 5 d, the PT group crossed the hole board randomly, whereas the T group gradually learned to orientate in the hole board. The mice were killed 24 hr after the last performance. A shift in 36G9-ir appeared from the cell somata to the dendrites of hippocampal principal neurons when comparing the H and PT group, respectively. In contrast, the T group showed strong PKCγ-ir in both cell somata and dendrites, which clearly exceeded that of the H and PT mice. In this way, 36G9-ir reveals the physiologically activated neurons involved in hole board learning. The present results, showing changes in PKCγ-ir and redistribution of hippocampal PKCγ induced by hole board learning, are consistent with the observation that PKC is involved in spatial memory processes.

Aromatase Activity in the Preoptic Area Differs Between Aggressive and Nonaggressive Male House Mice

Treatment with testosterone (T) or estradiol (E2) facilitates intraspecific aggressive behavior in adult rodents. Brain aromatization of T to E2 appears to be involved in facilitation of fighting behavior. In the present study we measure the in vitro brain aromatase activity (AA) in the preoptic area (POA), amygdaloid nuclei (Am), ventromedial hypothalamus (VMH), and parietal cortex (CTX) from two strains of adult male house mice, which were genetically selected for territorial aggression, based upon their attack latencies (short attack latency: SAL; long attack latency: LAL). The results reveal a higher AA in the POA of nonaggressive LAL males, as compared to aggressive SAL animals. The POA AA is, thus, inversely correlated with aggressiveness. The AA levels in both the VMH and Am do not differ significantly between strains. Furthermore, a differential brain area-specific AA distribution exists: POA > VMH AA in LAL, whereas POA < VMH in SAL. In both selection lines, the Am exhibits the highest levels of AA, as compared to the other investigated areas. Kinetic studies revealed that the aromatase Km is similar in both strains. The results indicate that the strain difference in AA is specific to the POA, but is not necessarily positivefy correlated with circulating plasma T levels. Other factors, in addition to androgen, are probably involved in the regulation of POA aromatase. We suggest that a higher neural androgen receptor sensitivity exists in the POA of nonaggressive LAL males, resulting in higher adult POA AA, despite lower concentrations of circulating T.