Dysregulated zinc homeostasis and microadenomas in the anterior pituitary: pathological insights into suicide risk.

Background: Suicide is a significant public health problem influenced by various risk factors, including dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. Zinc (Zn), essential for pituitary function in hormone synthesis and release, has been linked to suicide, with studies noting reduced serum levels and altered brain transport mechanisms. Despite Zn's crucial role in pituitary function and its involvement in suicidal behavior, information on pituitary Zn in suicide is scarce. Tumor cells modify Zn dynamics in tissues, and a previous report suggests microadenomas in the anterior pituitary as a risk factor for suicide. Methods: Histopathological analysis with hematoxylin-eosin stain and histochemical techniques to assess Zn homeostasis were carried out on anterior pituitary postmortem samples from 14 suicide completers and 9 non-suicidal cases. Results: Pituitary microadenomas were identified in 35% of suicide cases and none in the non-suicidal cases. Furthermore, compartmentalized Zn (detected via dithizone reactivity), but not free Zn levels (detected via zinquin reactivity), was lower in the suicide cases compared to the non-suicidal group. Conclusion: This is the first report of a potential association between disrupted Zn homeostasis and microadenomas in the anterior pituitary as a feature in suicide and provides critical insights for future neuroendocrine Zn-related research.

Increased cell number with reduced nitric oxide level and augmented superoxide dismutase activity in the anterior-pituitary region of young suicide completers.

Suicidal behavior is a complex human behavior and current data suggests that suicide is an increasing cause of death among young people. The neurobiology of suicide is unknown and data investigating the role of the pituitary in suicidal behavior is scarce. Imaging data suggests that this gland increases in size in patients with major depression and recent data implicates hyperactivity of the hypothalamus-pituitary-adrenal axis in suicidal behavior. In this study, we evaluate the size and number of cells as well as markers related to oxidative stress and lipid peroxidation of the anterior and posterior sections of the pituitary gland of male suicide completers. Stereological analysis is used to quantify the total cell number in anterior- and posterior-pituitary regions. We examined nitric oxide (NO) levels, Zinc (Zn) levels, superoxide dismutase (SOD) activity, 4-hydroxy-alkenals (4-HDA), malondialdehyde (MDA) and metallothioneins (MTs). Our results indicate that the anterior-pituitary region of suicide completers exhibits increased weight, likely due to an enhanced number of cells compared to the control group. In addition, we found a reduction of NO levels with higher SOD activity in the anterior-pituitary region of suicide victims. No changes in Zn, MDA, MTs, 4-HDA or MDA were observed in tissue of suicide completers compared to the control group. This study demonstrates that there is an increased number of cells, with an imbalance in oxidative stress without a process of lipid peroxidation in the anterior-pituitary region of young male suicide completers.

Neonatal ventral hippocampus lesion induces increase in nitric oxide [NO] levels which is attenuated by subchronic haloperidol treatment.

Haloperidol is a potent dopamine receptor antagonist and used to treat psychotic disorders, such as schizophrenia. Recent clinical and preclinical studies demonstrated the overactivity of the nitric oxide (NO) system in schizophrenia. Neonatal ventral hippocampal (nVH) lesions in rats have been widely used as a neurodevelopmental model that mimics schizophrenia-like behaviors. Here, we investigate first whether the nVH lesion causes changes in NO levels in different limbic brain regions in young adults, postnatal day (PD) 81, and second, whether haloperidol treatment from PD60 to PD81 reverses these changes, by determining the accumulation of nitrites. The results show that NO levels at the level of the prefrontal cortex, occipital cortex, and cerebellum are higher in the nVH lesion animals, and that the haloperidol, in part, attenuates these altered NO levels. The NO levels observed in the nVH lesion animals with and without haloperidol treatment may be relevant to behaviors observed in schizophrenia.