Gender and age-related variation in adenylyl cyclase activity in the human prefrontal cortex, hippocampus and dorsal raphe nuclei

Palego, Lionella; Giromella, Annalisa; Mazzoni, Maria Rosa; Marazziti, Donatella; Naccarato, Antonio Giuseppe; Giannaccini, Gino; Cassano, Giovanni Battista; Lucacchini, Antonio

doi:10.1016/s0304-3940(99)00952-0

Cited by 6 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our earlier work with the OBX model and with chemical lesions of monoamine systems, we found heterologous changes in AC signaling that differed with age (Slotkin et al, , 2000a: in young animals, the lesions elicited global induction of AC itself, and a consequent increase in stimulatory responses to norepinephrine and dopamine; in aging animals, these changes were either absent or in some brain regions, opposite to those seen in young animals, and were superimposed on the general increase in AC activity associated with aging by itself (Palego et al, 2000;Slotkin et al, 1999b). Similarly, the current results for 5HT cell signaling are consonant with Figure 1 Effects of OBX on 5HT 1A (a) and 5HT 2 (b) receptor binding.…”

Section: Discussionmentioning

confidence: 81%

Serotonergic Cell Signaling in an Animal Model of Aging and Depression: Olfactory Bulbectomy Elicits Different Adaptations in Brain Regions of Young Adult vs Aging Rats

Slotkin

Cousins

Tate

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Aging involves neuronal and synaptic loss, and maintenance of function depends on adaptations in cellular responsiveness. We studied olfactory bulbectomy (OBX), a model that recapitulates monoaminergic dysfunction in depression, in 10-week vs 19-month-old rats, and evaluated 5HT (5-hydroxytryptamine, serotonin) mechanisms. OBX elicited little change in 5HT1A receptors in the cerebral cortex or striatum of either age group. In contrast, 5HT2 receptors showed disparate effects, with a decrease in the cerebral cortex of young OBX but not aging OBX rats, whereas the latter group showed a selective decrease in striatal 5HT2 receptors. Greater differences were apparent for 5HT-mediated cell signaling, assessed for the adenylyl cyclase (AC) cascade. In young animals, 5HT had a stimulatory effect on AC that was unaltered by OBX. However, in aging animals, the pattern of 5HT responses showed marked alterations in response to OBX: under basal conditions, stimulatory effects were enhanced but when AC was activated with forskolin, 5HT became markedly inhibitory in the striatum of aged OBX animals. Assessment of the relative AC responses to two direct stimulants that act on different epitopes of the enzyme, forskolin and Mn2+, pointed to a shift in the AC isoform and/or its ability to associate with G-proteins as the mechanism underlying the age-related differences for OBX effects. These data indicate that there are biological distinctions in the response of 5HT systems to OBX in young adult vs aging animals, which, if present in geriatric depression, could provide a mechanistic basis for differences in responses to antidepressants that act on 5HT.

show abstract

Section: Discussionmentioning

confidence: 81%

Serotonergic Cell Signaling in an Animal Model of Aging and Depression: Olfactory Bulbectomy Elicits Different Adaptations in Brain Regions of Young Adult vs Aging Rats

Slotkin

Cousins

Tate

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…Reduction and/or alteration in olfactory function may also be due to changes at the level of the receptor cell. For instance, a age-related loss of selectivity was observed in a study of odorant response characteristics of ORNs dissociated from biopsies (114), and age-related changes in ion channel distribution (111,112), or other components of the intracellular signaling cascades (113) could result in receptor cell dysfunction. Although the extent of olfactory epithelium is reduced with aging (21, 98), it remains unclear whether this accounts for agerelated olfactory loss, as studies indicate that olfactory function is not affected even with substantial reduction of olfactory epithelial area (21, 22).…”

Section: Age Associated Olfactory Lossmentioning

confidence: 99%