Pierrette Gaudreau

Autoradiographic distribution of [3H]neurotensin receptors in rat brain: Visualization by tritium-sensitive film

[3H]Neurotensin ([3H]NT) binds specifically to a single class of binding sites on slides-mounted sections of rat brain 1Kp = 5.1 nM; Bmax = 16.2 fmol/mg tissue). Bound [3H]NT can be displaced by nonradioactive NT and a series of its fragments and analogues with relative potencies that correlate closely (r = 0.89; p less than 0.01) to their potencies in the rat stomach strip bioassay. These results suggest that NT receptors are similar in both systems. [3H]NT binding sites were visualized by using tritium-sensitive LKB film analysed by computerized densitometry. [3H]NT receptors are highly concentrated in the external layer of the olfactory bulb, in the rhinal sulcus, in certain nuclei of the amygdala, in the substantia nigra, zona compacta and in the ventral tegmental area. The high density of [3H]NT receptors in the last two areas suggest an interaction between NT and brain dopaminergic systems such as the nigrostriatal and the mesolimbic pathways.

Characterization and visualization of cholecystokinin receptors in rat brain using [3H]pentagastrin

[3H]Pentagastrin binds specifically to an apparent single class of CCK receptors on slide-mounted sections of rat brain (KD = 5.6 nM; Bmax = 36.6 fmol/mg protein). This specific binding is temperature-dependent and regulated by ions and nucleotides. The relative potencies of C-terminal fragments of CCK-8(SO3H), benzotript and proglumide in inhibiting specific [3H]pentagastrin binding to CCK brain receptors reinforce the concept of different brain and pancreas CCK receptors. CCK receptors were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry. CCK receptors are highly concentrated in the cortex, dentate gyrus, granular and external plexiform layers of the olfactory bulb, anterior olfactory nuclei, olfactory tubercle, claustrum, accumbens nucleus, some nuclei of the amygdala, thalamus and hypothalamus.

Dopamine D-5 receptor modulates hippocampal acetylcholine release.

Dopamine is intimately involved in cognitive processes in the brain. Of the several subtypes of dopamine receptors, the possible role of dopamine D1-like receptors in brain functions, especially in learning and memory, has recently generated much interest. However, molecularly the D1-like receptors are comprised of at least two subtypes, namely D-1 and D-5, and it has not been possible to ascertain which of these two receptor classes is responsible for these functions due to the lack of selective ligands. In the present study, utilizing a combined antisense-in vivo dialysis approach, we show that the D-5 subtype is the dopamine D1-like receptor involved in modulating hippocampal acetylcholine (ACh) release, a transmitter implicated in a variety of cognitive processes. This is one of the first evidence for a functional role for the D-5 receptor.

Possible interactions between dynorphin and dopaminergic systems in rat basal ganglia and substantia nigra

Chronic haloperidol treatment markedly increases dynorphin-related peptide contents in caudate-putamen, globus pallidus and substantia nigra. Leu-enkephalin levels follow dynorphin-related peptide concentrations in these areas while Met-enkephalin-related peptide contents are unchanged in the substantia nigra following a similar treatment. An acute haloperidol injection had no effect on any opioid peptide levels in the basal ganglia. This suggests that Leu-enkephalin is likely to be derived from prodynorphin in the rat striatonigral pathway. Moreover, the Leu-enkephalin/dynorphin projection appears to be under striatal dopaminergic control.

Trajectories of Physical Function Decline and Psychological Functioning: The Québec Longitudinal Study on Nutrition and Successful Aging (NuAge)

BACKGROUND Decline of physical function with age is associated with substantial health consequences. Physical and psychological functioning is linked, but the temporal nature of this association remains unclear. METHODS Three-year follow-up data from men and women (n = 1,741), aged 68-82 years, in the longitudinal study on nutrition and successful aging (NuAge; Québec, Canada) were used. Growth curve modeling was performed to examine trajectories of a global physical performance score across time as conditioned by cognition and depression. RESULTS Significant decline in physical function was observed (p < .0001). Rate of decline in physical performance score was accelerated in the older participants (>77 years; age(2): p < .01) but not affected by slight decline in cognition or depression. Yet, people with lower cognition level and more depressive symptoms show lower physical capacity throughout the entire follow-up period (p < .0001). CONCLUSIONS Physical function significantly declined over 3 years, in particular in the oldest group. A subtle decline in psychological health paralleled decline in physical function but did not accelerate it.

Mechanisms underlying the neuroprotective effect of brain reserve against late life depression.

Depression is common and medically relevant illness that has been associated to a state of “accelerated aging” and can significantly compromise successful aging. In recent years, the concept of “brain reserve” has emerged to describe some individuals having an increased “baseline adaptive neuroplasticity”, providing greater dynamic capacity for adjusting and remodeling cortical circuits to various stressors. We hypothesize that brain reserve may have neuroprotective effects against late life depression. Here, we discuss the modulatory capacity of stress and corticosteroid hormones on hippocampal plasticity and neuronal viability in late life depression as well as the anti-depressive of ketamine and scopolamine mediated by stimulation of the mammalian target of rapamycin, increased inhibitory phosphorylation of GSK-3β, and increased synaptogenesis. This review shall shed light on complex neurobiological mechanisms that underpin late life depression and help to better understand neural correlates of resilience. Investigating how rat models of increased cognitive reserve mitigate a chronic mild stress-elicited depression will afford new insights in the search for new therapeutic targets to treat this neuropsychiatric disorder.

Influence of age and sex on basal secretion of growth hormone (GH) and on GH-induced release by porcine GH-releasing factor pGRF(1-29NH2) in growing pigs.

The aim of this study was to determine the effect of age and sex on basal secretory patterns of growth hormone (GH) and growth hormone-releasing factor (GRF) induced GH release. Eighteen pigs (9 castrated males and 9 females) were stimulated with pGRF(1-29)NH2 at 7,11,15,19 and 23 weeks of age. Blood samples were taken from each animal via jugular vein cannulae every 20 min, from 6 hr before to 5 hr after iv GRF administration at a dose of 4 micrograms/kg. GH baseline levels, amplitude of the GH peaks, area under the GH peaks and the overall mean of GH serum levels decreased (P less than .001) with age in both sexes. Age also had a marked effect on GRF-induced GH release: the amplitude of GH peaks and area under the GH peaks decreased (P less than .001) with age. The GH response to pGRF(1-29)NH2 varied considerably, depending on the timing of the episodic endogenous secretion of GH. An immediate response (less than 30 min) was observed when GRF was injected at the end of a trough period or at the beginning of a peak, but there was no immediate response when GRF was injected at the end of a peak or at the beginning of a trough period. Our results show that both endogenous GH secretion and pGRF(1-29)NH2-induced GH release declines with age, suggesting a decreased sensitivity of the somatotroph cells to GRF with age; and that the high variability of the GH response to pGRF(1-29)NH2 stimulation depends greatly on the timing of the episodic endogenous GH release, thus implying a possible episodic endogenous somatostatin secretion by the hypothalamus.

Diet quality and cognition among older adults from the NuAge study.

BACKGROUND AND OBJECTIVES A healthy diet may prevent cognitive decline either directly, or by decreasing risk of nutrition-related chronic diseases associated with cognitive decline. This study examined the relationships between diet quality (DQ) and cognition for over 3 years among 1488 older adults (52.6% female) from the NuAge study, aged 67 to 84 years at recruitment. METHODS Cognition was assessed at four annual visits using the modified mini-mental status examination (3MS); rate of cognitive decline was computed for each participant over the 3 years of follow-up using mixed model analyses and the individual-specific number of months between 3MS assessments. Dietary data were collected at recruitment using a validated 78-item, semi-quantitative food frequency questionnaire (FFQ). DQ was characterized as the Canadian Healthy Eating Index (C-HEI), a 9-component global DQ index (maximum score=100) computed from the FFQ output. Other variables were collected by questionnaire or direct measurement. Multivariate analyses were carried out to assess the association of DQ controlled for confounders on cognition. RESULTS Total C-HEI was better in females (78.7±9.1 vs 75.7±9.4, p<.0001) as were C-HEI component subscores. Males, the less educated, smokers, those with poor social engagement, symptoms of depression, a higher waist:hip ratio and who reported financial insecurity had a poor quality diet that could contribute to chronic diseases associated with cognition. Along with functional autonomy, most of these variables emerged as covariates of baseline 3MS and predictors of cognitive decline. While certain C-HEI subscores and total C-HEI were positive univariate correlates of 3MS at recruitment, total DQ was not associated with cognition in multivariate analyses, either at baseline or over 3 years of follow-up. CONCLUSIONS DQ was not independently associated with cognition. However, the study demonstrates relationships between diet quality and risk factors for chronic diseases associated with cognition. Consequently, older adults might benefit from a healthy diet to decrease risk of nutrition-related chronic diseases established as risk factors for cognitive decline. Further work in diverse older populations, use of dietary data collected earlier in life, finer cognitive measures and longer follow-up are necessary to better elucidate relationships between diet quality, chronic diseases and cognition.

Baseline determinants of global diet quality in older men and women from the NuAge cohort

Judicious food choices are of prime importance during aging.ObjectivesThis study was conducted to identify individual and collective attributes determining global diet quality (DQ).MethodologyParticipants were 1,793 adults (52% women) from the NuAge study on nutrition and successful aging. Subjects aged 67 to 84 years in relatively good health were recruited from the Québec Medicare Database. Sociodemographic, affective, and cognitive data, health conditions, perceived physical health and functional status, dietary habits and dietary attributes and community resources were obtained using questionnaires. Body weight and height were measured and body mass index (BMI) was calculated. Three non-consecutive 24-hour diet recalls were collected at recruitment. DQ, assessed using the Canadian Healthy Eating Index (C-HEI, /100), was computed on the mean intakes from the diet recalls. Analyses were stratified by gender. Variables significantly related to DQ in bivariate analyses (p<.05) were entered into backward stepwise multiple regression analyses.ResultsAmong men, the final model showed higher education (β=0.23, p=.01), diet knowledge (β=0.96, p<.0001), number of daily meals (β=1.91, p=.02) and perceived physical health (β=0.06, p=.01) to be positive determinants of DQ, whereas alcohol consumption (β=−2.25, p=.05), wearing dentures (β=−2.31, p=.01) and eating regularly in restaurants (β=− 1.65, p=.03) were negative determinants of DQ (adjusted R2 = 13.7%). Among women, higher education (β=0.29, p=.002), diet knowledge (β=0.54, p=.002), number of daily meals (β=3.61, p<.0001), and hunger (β=0.61, p<.0001) were positive determinants of global DQ; greater BMI (β=−0.16, p=.03) and chewing problems (β=−0.48, p=.03) were negative determinants of DQ (adjusted R2 = 7.8%).DiscussionThese results point to several key factors influencing global DQ in older adults and also show gender-based differences. More research must be done to better understand how these factors change with aging and exert their impact on diet, particularly since variance in DQ was largely unexplained. As diet knowledge was an independent predictor for both genders, targeted, sustainable interventions are needed to ensure good diet quality as people age.

DYNAMICS OF GROWTH HORMONE RESPONSIVENESS TO GROWTH HORMONE RELEASING FACTOR IN AGING RATS PERIPHERAL AND CENTRAL INFLUENCES

The in vivo and in vitro dynamics of somatotroph responsiveness to rGRF (1-29) NH2 (rat growth hormone releasing factor) were evaluated in 2-, 4-, 8-, 12-, and 20-month-old male rats. In vivo, using pentobarbital-anesthetized animals, we observed that the rGH (rat growth hormone) responsiveness to 0.4 and 1.6 micrograms/kg rGRF started to decline at the higher dose in 12-month-old rats and was completely blunted at both rGRF doses in 20-month-old animals. In vitro, using freshly dispersed perifused pituitary cells, we also documented a decrease of rGRF-induced rGH secretion in 12- and 20-month-old rats. Moreover, as the animals aged, the rGRF-induced rGH secretion was differentially affected by the inhibiting action of somatostatin (p less than 0.001), suggesting a loss of pituitary sensitivity to somatostatin in the presence of a high concentration of rGRF. The pituitary rGH content increased until rats reached 12 months of age, but was diminished in 20-month-old rats. In contrast, the pituitary somatostatin content increased twofold in 20-month-old rats as compared with younger rats. The hypothalamic somatostatin content was highest in 8-month-old rats and only slightly diminished in 20-month-old animals. Finally, plasma insulin-like growth factor I concentrations were highest in 8-month-old rats and lowest in 20-month-old animals. Altogether, these results indicate that the physiological loss of somatotroph responsiveness associated with the process of aging starts around 12 months of age.(ABSTRACT TRUNCATED AT 250 WORDS)