There have been enough cell death modes delineated in the biomedical literature to befuddle all cell death researchers. Mulling over cell death from the viewpoints of the host tissue or organ and of the host animal, we construe that there should be only two physiological cell death modes, i.e. apoptosis and senescent death (SD), as well as two pathological modes, i.e. necrosis and stress-induced cell death (SICD). Other death modes described in the literature are ad-hoc variants or coalescences of some of these four basic ones in different physiological or pathological situations. SD, SICD and necrosis kill useful cells and will thus trigger regeneration, wound healing and probably also scar formation. SICD and necrosis will likely instigate inflammation as well. Apoptosis occurs as a mechanism to purge no-longer useful cells from a tissue via phagocytosis by cells with phagocytic ability that are collectively tagged by us as scavengers, including macrophages; therefore apoptosis is not followed by regeneration and inflammation. The answer for the question of “who dies” clearly differentiates apoptosis from SD, SICD and necrosis, despite other similarities and disparities among the four demise modes. Apoptosis cannot occur in cell lines in vitro, because cell lines are immortalized by reprogramming the death program of the parental cells, because in culture there lack scavengers and complex communications among different cell types, and because culture condition is a stress to the cells. Several issues of cell death that remain enigmatic to us are also described for peers to deliberate and debate.

Background: There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction. Methods: Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio. Results: In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups. Conclusions: These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be germane to understanding this relationship in humans.

The neurological correlates of Generalised Anxiety Disorder (GAD) are not well known, however there is evidence of cortical dysregulation in patients with GAD. The aim of the study was to examine cortical functional activity in different cerebral regions in patients with GAD using electroencephalogram (EEG) nonlinear analysis to evaluate its contribution of anxiety severity. The cohorts consisted of 64 patients diagnosed with GAD as classified by the Structured Clinical Interview for the Diagnostic and Statistical Manual of the American Psychiatric Association-IV-TR. Anxiety severity was assessed using the Hamilton Rating Scale for Anxiety (HAMA) severity score, with 7 ≤ scores ≤ 17 indicating mild anxiety as A group (n = 31) and 18 and above indicating moderate-severe anxiety as B group (n = 33). Participants with clinical levels of depression symptoms were excluded. A healthy control group comprising 30 participants was matched for age and gender. Closed eyes EEGs were conducted, and between-group differences on non-linear parameter Correlation Dimension (D2) were analyzed. The association of D2 value with HAMA scores was analyzed using multiple linear stepwise regression. Compared with the control group, D2 values were increased in anxiety groups (P < .05). For those with mild anxiety, this difference occurred in the left prefrontal regions (P < .05). For those with moderate-severe anxiety, significantly greater D2 values were observed in all of the cerebral regions, especially in the left cerebral regions and right temporal lobe (P < .01). When compared with those with mild anxiety, D2 values were significantly greater for those with moderate-severe anxiety in the right temporal lobe and all left cerebral regions except for left occipital lobe (P < .05). A positive correlation was observed between D2 values and moderate-severe anxiety HAMA scores. The increased D2 values were found in the majority of cerebral regions in GAD patients, especially in the left cerebral regions and the right temporal lobe. The increased GAD severity positively correlates to the D2 values in a larger number of cerebral regions. This analysis method can potentially be used as a complementary tool to examine dysfunctional cortical activity in GAD.

While there is evidence that the development and course of major depressive disorder (MDD) symptomatology is associated with vascular disease, and that there are changes in energy utilization in the disorder, the extent to which cerebral blood flow is changed in this condition is not clear. This study utilized a novel imaging technique previously used in coronary and stroke patients, 320-slice Computed-Tomography (CT), to assess regional cerebral blood flow (rCBF) in those with MDD and examine the pattern of regional cerebral perfusion. Thirty nine participants with depressive symptoms (Hamilton Depression Rating Scale 24 (HAMD24) score >20, and Self-Rating Depression Scale (SDS) score >53) and 41 healthy volunteers were studied. For all subjects, 3 ml of venous blood was collected to assess hematological parameters. Trancranial Doppler (TCD) ultrasound was utilized to measure parameters of cerebral artery rCBFV and analyse the Pulsatility Index (PI). 16 subjects (8 = MDD; 8 = healthy) also had rCBF measured in different cerebral artery regions using 320-slice CT. Differences among groups were analyzed using ANOVA and Pearson's tests were employed in our statistical analyses. Compared with the control group, whole blood viscosity (including high\middle\low shear rate)and hematocrit (HCT) were significantly increased in the MDD group. PI values in different cerebral artery regions and parameters of rCBFV in the cerebral arteries were decreased in depressive participants, and there was a positive relationship between rCBFV and the corresponding vascular rCBF in both gray and white matter. rCBF of the left gray matter was lower than that of the right in MDD. Major depression is characterized by a wide range of CBF impairments and prominent changes in gray matter blood flow. 320-slice CT appears to be a valid and promising tool for measuring rCBF, and could thus be employed in psychiatric settings for biomarker and treatment response purposes.

Accumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD.