Search

Neurofibrillar tangles made up of 'paired helical filaments' (PHFs) consisting of hyperphosphorylated microtubule-associated protein tau are major hallmarks of Alzheimer's disease (AD). Tangle formation selectively affects certain neuronal types and systematically progresses throughout numerous brain areas, which reflects a hierarchy of neuronal vulnerability and provides the basis for the neuropathological staging of disease severity. Mechanisms underlying this selective neuronal vulnerability are unknown. We showed previously that reversible PHF-like phosphorylation of tau occurs during obligate hibernation. Here we extend these findings to facultative hibernators such as Syrian hamsters (Mesocricetus auratus) forced into hibernation. In this model, we showed in the basal forebrain projection system that cholinergic neurons are selectively affected by PHF-like phosphorylated tau, while gamma-aminobutyric acid (GABA)ergic neurons are largely spared, which shows strong parallels to the situation in AD. Formation of PHF-tau in these neurons apparently does not affect their function as pacemaker for terminating hibernation. We conclude that although formation of PHF-like phosphorylated tau in the mammalian brain follows a certain hierarchy, affecting some neurons more frequently than others, it is not necessarily associated with impaired neuronal function and viability. This indicates a more general link between PHF-like phosphorylation of tau and the adaptation of neurons under conditions of a 'vita minima'.

Neurofibrillar tangles made up of 'paired helical filaments' (PHFs) consisting of hyperphosphorylated microtubule-associated protein tau are major hallmarks of Alzheimer's disease (AD). Tangle formation selectively affects certain neuronal types and systematically progresses throughout numerous brain areas, which reflects a hierarchy of neuronal vulnerability and provides the basis for the neuropathological staging of disease severity. Mechanisms underlying this selective neuronal vulnerability are unknown. We showed previously that reversible PHF-like phosphorylation of tau occurs during obligate hibernation. Here we extend these findings to facultative hibernators such as Syrian hamsters (Mesocricetus auratus) forced into hibernation. In this model, we showed in the basal forebrain projection system that cholinergic neurons are selectively affected by PHF-like phosphorylated tau, while gamma-aminobutyric acid (GABA)ergic neurons are largely spared, which shows strong parallels to the situation in AD. Formation of PHF-tau in these neurons apparently does not affect their function as pacemaker for terminating hibernation. We conclude that although formation of PHF-like phosphorylated tau in the mammalian brain follows a certain hierarchy, affecting some neurons more frequently than others, it is not necessarily associated with impaired neuronal function and viability. This indicates a more general link between PHF-like phosphorylation of tau and the adaptation of neurons under conditions of a 'vita minima'.

Oxytocin (OXT) has been implicated in the regulation of social behaviors, including intermale offensive aggression. Recently, we showed that acute enhancement of brain OXT levels markedly suppressed offensive aggression and increased social exploration in resident rats confronted with an intruder in their home territory. Moreover, a different responsivity to the exogenous OXTergic manipulation was observed among individuals based on their baseline aggression. In this study we aimed at evaluating the behavioral response to chronically enhancing or attenuating central OXT levels, and at scrutinizing whether the trait-aggression moderates the treatment-induced behavioral changes. To this end, resident male wild-type Groningen rats were continuously (via osmotic minipumps) intracerebroventricularly infused with synthetic OXT or a selective OXT receptor (OXTR) antagonist for 7days. Changes in behavior were assessed performing a resident-intruder test before and at the end of the treatment period, as well as after 7days of withdrawal. Chronic infusion of OXT was found to selectively suppress aggression and enhance social exploration. Chronic blockage of OXTRs instead increased introductory aggressive behavior (i.e. lateral threat), yet without affecting the total duration of the aggression. The magnitude of the anti-aggressive changes correlated positively with the level of baseline aggression. Interestingly, OXT-induced behavioral changes persisted 7days after cessation of the treatment. In conclusion, these findings provide further evidence that enhanced functional activity of the central OXTergic system decreases social offensive aggression while it increases social explorative behavior. The data also indicate that chronically enhancing brain OXT levels may cause enduring anti-aggressive and pro-social explorative behavioral effects.

In this experiment we investigate the effect of photoperiod on locomotor activity, body mass, food intake, growth efficiency (relationship between body mass change and food intake), energy expenditure, and body composition in growing Wistar rats. Two groups of animals were subjected to either a long, LD 18:6 (II = 8), Or Short photoperiod, LD 6:18 (n = 7), during a period of 190 days after weaning. Activity, body mass, food intake, and energy expenditure were measured during the study, as well as body composition at the end of the experiment. We show that growing rats exposed to short photoperiods (a) have a lower rate of weight gain, (b) have similar energy intakes, (c) have lower growth efficiency, (d) have lower daily energy expenditure and resting metabolic rate, and (e) gain less lean body mass than those exposed to long photoperiods. We suggest that the distribution of energy expenditure and food intake over the total 24-h cycle may be responsible for the differences in body weight gain between the two photoperiods. (C) 1997 Elsevier Science Inc.

Neurofibrillar tangles made up of 'paired helical filaments' (PHFs) consisting of hyperphosphorylated microtubule-associated protein tau are major hallmarks of Alzheimer's disease (AD). Tangle formation selectively affects certain neuronal types and systematically progresses throughout numerous brain areas, which reflects a hierarchy of neuronal vulnerability and provides the basis for the neuropathological staging of disease severity. Mechanisms underlying this selective neuronal vulnerability are unknown. We showed previously that reversible PHF-like phosphorylation of tau occurs during obligate hibernation. Here we extend these findings to facultative hibernators such as Syrian hamsters (Mesocricetus auratus) forced into hibernation. In this model, we showed in the basal forebrain projection system that cholinergic neurons are selectively affected by PHF-like phosphorylated tau, while gamma-aminobutyric acid (GABA)ergic neurons are largely spared, which shows strong parallels to the situation in AD. Formation of PHF-tau in these neurons apparently does not affect their function as pacemaker for terminating hibernation. We conclude that although formation of PHF-like phosphorylated tau in the mammalian brain follows a certain hierarchy, affecting some neurons more frequently than others, it is not necessarily associated with impaired neuronal function and viability. This indicates a more general link between PHF-like phosphorylation of tau and the adaptation of neurons under conditions of a 'vita minima'.

The suprachiasmatic nucleus (SCN) is engaged in modulation of memory retention after (fear) conditioning, but it is unknown which pathways and neurotransmitter system(s) play a role in this action. Here we examine immunocytochemically whether muscarinic acetylcholine receptors (mAChRs), mediating cholinergic signal transduction in the SCN, are involved. For this purpose, mAChR immunoreactivity (mAChR-ir) was studied in the SCN after various stages of passive shock avoidance (PSA) and active shock avoidance (ASA) training and, for ASA, at various posttraining time points. mAChR-ir was significantly enhanced in SCN neurons as a result of the training procedure, and the number of mAChR-positive glial cells in the SCN increased significantly. The increase in mAChR-ir as a result of PSA and ASA training was not due to fear conditioning or the number of correct avoidances (in case of ASA training) but rather to behavioral arousal as a consequence of (brief) exposure to a novel environment (the test apparatus). This finding was confirmed by a cage-change experiment in which the rats were allowed to stay in a novel cage for 15 min or 24 hr. Only the brief exposure to the fresh cage triggered alterations for SCN mAChRs 24 hr later. These results shed new light on a possible function of the cholinergic system in the SCN mediated by mAChRs in relation to modulation of memory processes and demonstrate that behavioral arousal during (the habituation stage of) a learning task is sufficient to alter the mAChR system in the SCN. (C) 2004 Wiley-Liss, Inc.

Active shock avoidance was used to explore the impact of behavioural stimulation on the neurochemistry of the suprachiasmatic nucleus. We have found previously that the expression of muscarinic acetylcholine receptors in the suprachiasmatic nucleus of young rats was significantly enhanced 24 hours after fear conditioning. Here, we investigated whether this observation is age-dependent. We used 26 month-old Wistar rats with a deteriorated circadian system, and compared them with young rats (4 months of age) with an intact circadian system. Vasopressin, representing a major output system of the suprachiasmatic nucleus, was studied in addition to muscarinic receptors. Young rats showed a significant increase in immunostaining for muscarinic acetylcholine receptors 24 h after training, corroborating earlier observations. Aged rats did not show such an increase. In contrast, aged rats did show an increase in vasopressin immunoreactivity 24 h after fear conditioning, both at the level of content and cell number, while young rats did not reveal a significant rise. Thus, it seems that these two neurochemical systems in the suprachiasmatic nucleus are regulated independently. The results further demonstrate that the circadian pacemaker is influenced by fear conditioning in an age-dependent manner.

Entrainment by nonphotic, activity-inducing stimuli has been investigated in detail in nocturnal rodents, but little is known about nonphotic entrainment in diurnal animals. Comparative studies would offer the opportunity to distinguish between two possibilities. (1) If nonphotic phase shifts depend on the phase of the activity cycle, the phase response curve (PRC) should be about 180° out of phase in nocturnal and diurnal mammals. (2) If nonphotic phase shifts depend on the phase of the pacemaker, the two PRCs should be in phase. We used the diurnalEuropean ground squirrel ( Spermophilus citellus) in a nonphotic entrainment experiment to distinguish between the two possibilities. Ten European ground squirrels were kept under dim red light (