Histological characterization and quantification of newborn cells in the adult rodent brain.

This protocol describes the identification and characterization of newborn cells generated in the rodent brain after injury through birthdating with the thymidine analog 5-bromo-2'-deoxyuridine, followed by immunohistochemical labeling of fixed tissue sections. We also describe a software-assisted approach for automated detection and quantification of cells in large three-dimensional tissue volumes acquired using confocal microscopy. This approach facilitates the identification of low-frequency events that may be difficult to capture using manual counting methods, including stereology based on random sampling. For complete details on the use and execution of this protocol, please refer to Ermine et al. (2020).

The effect of angiotensin AT1A inactivation on innate and learned fear responses in mice and its relationship to blood pressure.

Angiotensin AT1 receptors are implicated in behavioral and physiological processes associated with fear and stress. However, the precise role of AT1 receptors in modulating fear-related behavior and its relation to their physiological effects remains unclear. Here, we examined innate and learned fear responses and their relationship to cardiovascular arousal in AT1A receptor knockout (AT1A-/-) mice. Using synchronized video and blood pressure telemetry, we found that, in a novel test environment, AT1A-/- mice showed reduced neophobia but a similar rise in blood pressure, as compared to AT1A+/+ mice. In response to a discrete threat, footshock, both flight behavior and cardiovascular arousal were decreased in AT1A-/- mice. Reduced flight behavior was also observed in AT1A-/- mice in the elevated T-maze test. During fear conditioning, the immediate freezing response to the first shock, but not the rate of freezing acquisition was decreased in AT1A-/- mice. Likewise, AT1A-/- mice showed reduced freezing and pressor responses to the first re-exposure, but normal rate of freezing extinction over subsequent trials. Similarly, in the elevated T-maze, the rates of avoidance acquisition and escape learning remained unchanged in AT1A-/- mice. Finally, after re-exposure, AT1A-/- mice displayed altered c-Fos expression, compared to AT1A+/+ mice, in the hypothalamus and periaqueductal gray but not in fear-related limbic-cortical areas, nor in medullary nuclei that convey visceral afferent information. We conclude that AT1A receptor knockout reduces innate fear responses, without affecting learning efficiency in mice. These effects are dissociable from cardiovascular effects and likely reflect altered neurotransmission in hypothalamic-midbrain defense regions.

Psychometric properties of the Cardiac Depression Scale: a systematic review.

BACKGROUND: The prevalence of depression is high in cardiac patients. Depression has a significant impact on quality of life, adherence to therapy, and an independent effect on prognosis. The Cardiac Depression Scale (CDS) is the only instrument designed to measure depression in cardiac patients. This study systematically reviewed the psychometric properties of the CDS for screening of depression in patients with coronary heart disease (CHD). METHODS: A search of MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Scopus and Web of Science was performed using the search term Cardiac Depression Scale in the title or abstract. Eligible studies were those that assessed reliability, validity or diagnostic accuracy of the CDS in patients with CHD. Methodological quality was assessed using the QUADAS-2 and STARD. RESULTS: Most studies assessed the reliability and validity of the CDS: three studies assessed construct validity using factor analysis; six studies assessed the validity of the CDS with other measures of depression; and four studies assessed its diagnostic accuracy. However, some studies reported overlapping samples, which reduces confidence in their evaluation. CONCLUSION: This review finds the CDS to be a psychometrically sound measurement instrument for identifying mild, moderate and severe depression in cardiac populations.

Depression and coronary heart disease: apprehending the elusive black dog.

Depression is the third leading cause of disease burden worldwide and is predicted to be the leading cause by 2030. Importantly, depression has been identified as an independent risk factor for coronary heart disease (CHD) and both share significant physiological overlap. Identification of depression is complex. Consequently, accurate diagnosis of comorbid depression and CHD is challenging and requires a move toward an interdisciplinary engagement of knowledge transfer. A concerted effort is required utilising translational research to better identify depression in the CHD population. This approach is not meant to categorise patients, rather it is aimed at progressing toward an improved prognosis. Further, this approach should provide health professionals with the confidence to apply the term depression and define its meaning in a more precise and consistent manner.

Role of angiotensin II Type 1A receptors in cardiovascular reactivity and neuronal activation after aversive stress in mice.

We determined whether genetic deficiency of angiotensin II Type 1A (AT(1A)) receptors in mice results in altered neuronal responsiveness and reduced cardiovascular reactivity to stress. Telemetry devices were used to measure mean arterial pressure, heart rate, and activity. Before stress, lower resting mean arterial pressure was recorded in AT(1A)(-/-) (85+/-2 mm Hg) than in AT(1A)(+/+) (112+/-2 mm Hg) mice; heart rate was not different between groups. Cage-switch stress for 90 minutes elevated blood pressure by +24+/-2 mm Hg in AT(1A)(+/+) and +17+/-2 mm Hg in AT(1A)(-/-) mice (P<0.01), and heart rate increased by +203+/-9 bpm in AT(1A)(+/+) and +121+/-9 bpm in AT(1A)(-/-) mice (P<0.001). Locomotor activation was less in AT(1A)(-/-) (3.0+/-0.4 U) than in AT(1A)(+/+) animals (6.0+/-0.4 U), but differences in blood pressure and heart rate persisted during nonactive periods. In contrast to wild-type mice, spontaneous baroreflex sensitivity was not inhibited by stress in AT(1A)(-/-) mice. After cage-switch stress, c-Fos immunoreactivity was less in the paraventricular (P<0.001) and dorsomedial (P=0.001) nuclei of the hypothalamus and rostral ventrolateral medulla (P<0.001) in AT(1A)(-/-) compared with AT(1A)(+/+) mice. Conversely, greater c-Fos immunoreactivity was observed in the medial nucleus of the amygdala, caudal ventrolateral medulla, and nucleus of the solitary tract (P<0.001) of AT(1A)(-/-) compared with AT(1A)(+/+) mice. Greater activation of the amygdala suggests that AT(1A) receptors normally inhibit the degree of stress-induced anxiety, whereas the lesser activation of the hypothalamus and rostral ventrolateral medulla suggests that AT(1A) receptors play a key role in autonomic cardiovascular reactions to acute aversive stress, as well as for stress-induced inhibition of the baroreflex.