Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression

AAV-Tau Mediates Pyramidal Neurodegeneration by Cell-Cycle Re-Entry without Neurofibrillary Tangle Formation in Wild-Type Mice

In Alzheimer's disease tauopathy is considered secondary to amyloid, and the duality obscures their relation and the definition of their respective contributions

Functional analysis of the leader peptide of the yeast gene CPA1 and heterologous regulation by other fungal peptides

The 25-amino-acid leader peptide present at the 5′ end of yeast CPA1 mRNA is responsible for the translational repression of that gene by arginine. We show here that the active domain of the yeast peptide is highly specific and extends over amino acids 6–23. The region between amino acids 6–21 is well conserved between similar peptides present upstream of CPA1-homologous genes in other fungi. The Neurospora crassa arg-2 peptide represses the expression of CPA1, whereas the peptide from Aspergillus nidulans has only a weak regulatory effect. Such results suggest that the N- and C-terminal amino acids of the peptide may influence its regulatory activity. We also show that the transcription start sites of CPA1 are not modified when the cells are grown in the presence of arginine, nor in a strain carrying an inactive peptide.Peer Reviewe

Adult neurogenesis and depression

<p>Adult neurogenesis (ANGE) is a process of generating new neurons in the brains of adult mammals, including humans. It takes place, e.g., in the subgranular zone of the dentate gyrus in the hippocampal formation. The function of the new neurons is not fully explained; however, they are considered to play an important role in learning and memory processes. There is also evidence that ANGE can mediate the response of hippocampal<br>formation to stress, preventing the onset of depression. Besides, newly-generated neurons seem to play an important role in therapeutic action of antidepressants (AD). Results from animal models and human studies, confirming and questioning the hypothesis of a key connection between depression and ANGE, are presented.<br>It is not clear whether the suppression of the production of new neurons influences the pathogenesis of depression and it seems that some other factors are more important. However, it is likely that the level of ANGE is important in treatment of at least some forms of depression. Several experiments, using animal models, have shown that AD, mood stabilizers or other depression therapies increase the level of ANGE. Also, blocking the generation of new neurons abolishes their therapeutic effect. Nevertheless, some recent publications question the significance of ANGE in AD action. The discrepancies described herein,<br>concerning the significance of ANGE in aetiology and treatment of depression, may reflect the complexity of the depressive disorder. This complexity is manifested by the different response (or no response) to various AD and other depression therapies in human patients.</p> <p> </p

Autophosphorylation at Thr 286 of the calcium-calmodulin kinase II in LTP

The calcium-calmodulin–dependent kinase II (CaMKII) is required for hippocampal longterm potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)– dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the �CaMKII gene that blocked the autophosphorylation of threonine at position 286 ( Thr 286) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N-methyl-D-aspartate receptor–dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of �CaMKII at Thr 286 appears to be required for LTP and learning. Long-lasting changes in synaptic strength (such as LTP) are thought to underlie learning and memory (1). Pharmacological and genetic lesions of CaMKII impair LTP and learning (2–4). Additionally, increasing the concentrations of constitutively activ

Rats that learn to vocalize for food reward emit longer and louder appetitive calls and fewer short aversive calls.

Rats are social animals that use ultrasonic vocalizations (USV) in their intraspecific communication. Several types of USV have been previously described, e.g., appetitive 50-kHz USV and aversive short 22-kHz USV. It is not fully understood which aspects of the USV repertoire play important functions during rat ultrasonic exchange. Here, we investigated features of USV emitted by rats trained in operant conditioning, is a form of associative learning between behavior and its consequences, to reinforce the production/emission of 50-kHz USV. Twenty percent of the trained rats learned to vocalize to receive a reward according to an arbitrarily set criterion, i.e., reaching the maximum number of proper responses by the end of each of the last three USV-training sessions, as well as according to a set of measurements independent from the criterion (e.g., shortening of training sessions). Over the training days, these rats also exhibited: an increasing percentage of rewarded 50-kHz calls, lengthening and amplitude-increasing of 50-kHz calls, and decreasing number of short 22-kHz calls. As a result, the potentially learning rats, when compared to non-learning rats, displayed shorter training sessions and different USV structure, i.e. higher call rates, more rewarded 50-kHz calls, longer and louder 50-kHz calls and fewer short 22-kHz calls. Finally, we reviewed the current literature knowledge regarding different lengths of 50-kHz calls in different behavioral contexts, the potential function of short 22-kHz calls as well as speculate that USV may not easily become an operant response due to their primary biological role, i.e., communication of emotional state between conspecifics