The contribution of rare SERPINA1 alleles into AATD should not be neglected in the diagnosis practice given there is a wide spectrum of variants originated by mutation and sometimes shuffled between chromosomes by recombination. Even though many of the rare variants are likely to be recent and population specific others seems to be as old as the Z allele and dispersed across European populations.

Stress or high levels of glucocorticoids (GCs) during developmental periods is known to induce persistent effects in the neuroendocrine circuits that control stress response, which may underlie individuals’ increased risk for developing neuropsychiatric conditions later in life, such as anxiety or depression. We developed a rat model (Wistar han) of mild exposure to unpredictable prenatal stress (PS), which consists in a 4-h stressor administered three times per week on a random basis; stressors include strobe lights, noise and restrain. Pregnant dams subjected to this protocol present disrupted circadian corticosterone secretion and increased corticosterone secretion upon acute stress exposure. Regarding progeny, both young adult (2 months old) male and female rats present increased levels of circulating corticosterone and hyperactivity of the hypothalamus-pituitary-adrenal axis to acute stress exposure. Both sexes present anxious- and depressive-like behaviors, shown by the decreased time spent in the open arms of the elevated plus maze (EPM) and in the light side of the light-dark box (LDB), and by increased immobility time in the forced swim test, respectively. Interestingly, these results were accompanied by structural modifications of the bed nucleus of stria terminalis (BNST) and hippocampus, as well as decreased norepinephrine and dopamine levels in the BNST, and serotonin levels in the hippocampus. In summary, we characterize a new model of mild PS, and show that stressful events during pregnancy can lead to long-lasting structural and neurochemical effects in the offspring, which affect behavior in adulthood.

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder. The neurodegeneration leading to incapacitating motor abnormalities mainly occurs in the nigrostriatal pathway due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Several animal models have been developed not only to better understand the mechanisms underlying neurodegeneration but also to test the potential of emerging disease-modifying therapies. However, despite aging being the main risk factor for developing idiopathic PD, most of the studies do not use aged animals. Therefore, this study aimed at assessing the effect of aging in the unilateral 6-hydroxydopamine (6-OHDA)-induced animal model of PD. For this, female young adult and aged rats received a unilateral injection of 6-OHDA into the medial forebrain bundle. Subsequently, the impact of aging on 6-OHDA-induced effects on animal welfare, motor performance, and nigrostriatal integrity were assessed. The results showed that aging had a negative impact on animal welfare after surgery. Furthermore, 6-OHDA-induced impairments on skilled motor function were significantly higher in aged rats when compared with their younger counterparts. Nigrostriatal histological analysis further revealed an increased 6-OHDA-induced dopaminergic cell loss in the SNpc of aged animals when compared to young animals. Overall, our results demonstrate a higher susceptibility of aged animals to 6-OHDA toxic insult.

Neurodegenerative disorders and traumatic events affecting the central nervous system (CNS) represent one of the main health problems nowadays. The level of disability and impairment of these patients is very high, both at physiological and psychological level, drastically altering a person's lifestyle. The fact that CNS tissue has a limited capacity of regeneration has hampered the development of possible therapies to these conditions. The specificity of each disease also increases the complexity of creating strategies capable of inducing significant recovery. Therefore, the search for a solution for these problems most likely demands a combinatorial approach that integrates knowledge from different fields. Tissue engineering and regenerative medicine (TERM) concepts merge areas such as biology, chemistry, physics, or biomaterials science, and it is a strong candidate for CNS applications. In particular, the development of cell and tissue instructive materials (CTIMs) can bring new opportunities for the treatment of these conditions. In this review, the authors summarize and discuss the most recent advances in the development of CTIMs for CNS applications, focusing on traumatic conditions such as spinal cord injuy, traumatic brain injuy, but also stroke, and other neurodegenerative diseases such as Alzheimer's and Parkinson's disease as well as multiple sclerosis.

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