Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

New neurons are continuously added to the dentate gyrus of the adult mammalian brain. During the critical period of a few weeks after birth when newborn neurons progressively mature, a restricted fraction is competitively selected to survive in an experience-dependent manner, a condition for their contribution to memory processes. The mechanisms that control critical stages of experience-dependent functional incorporation of adult newborn neurons remain largely unknown. Here, we identify a unique transcriptional regulator of the functional integration of newborn neurons, the inducible immediate early gene zif268/egr1. We show that newborn neurons in zif268-KO mice undergo accelerated death during the critical period of 2-3 wk around their birth and exhibit deficient neurochemical and morphological maturation, including reduced GluR1 expression, increased NKCC1/KCC2b chloride cotransporter ratio, altered dendritic development, and marked spine growth defect. Investigating responsiveness of newborn neurons to activity-dependent expression of zif268 in learning, we demonstrate that in the absence of zif268, training in a spatial learning task during this critical period fails to recruit newborn neurons and promote their survival, leading to impaired long-term memory. This study reveals a previously unknown mechanism for the control of the selection, functional maturation, and experience-dependent recruitment of dentate gyrus newborn neurons that depends on the inducible immediate early gene zif268, processes that are critical for their contribution to hippocampal-dependent long-term memory

Pre-hospital treatment of acute poisonings in Oslo

<p>Abstract</p> <p>Background</p> <p>Poisoned patients are often treated in and discharged from pre-hospital health care settings. Studies of poisonings should therefore not only include hospitalized patients. Aims: To describe the acutely poisoned patients treated by ambulance personnel and in an outpatient clinic; compare patients transferred to a higher treatment level with those discharged without transfer; and study the one-week mortality after pre-hospital discharge.</p> <p>Methods</p> <p>A one-year multi-centre study with prospective inclusion of all acutely poisoned patients ≥ 16 years of age treated in ambulances, an outpatient clinic, and hospitals in Oslo.</p> <p>Results</p> <p>A total of 3757 health service contacts from 2997 poisoning episodes were recorded: 1860 were treated in ambulances, of which 15 died and 750 (40%) were discharged without transfer; 956 were treated in outpatient clinic, of which 801 (84%) were discharged without transfer; and 941 episodes were treated in hospitals. Patients discharged alive after ambulance treatment were mainly poisoned by opiates (70%), were frequently comatose (35%), had respiratory depression (37%), and many received naloxone (49%). The majority of the patients discharged from the outpatient clinic were poisoned by ethanol (55%), fewer were comatose (10%), and they rarely had respiratory depression (4%). Among the hospitalized, pharmaceutical poisonings were most common (58%), 23% were comatose, and 7% had respiratory depression. Male patients comprised 69% of the pre-hospital discharges, but only 46% of the hospitalized patients. Except for one patient, who died of a new heroin overdose two days following discharge from an ambulance, there were no deaths during the first week after the poisonings in the 90% of the pre-hospital discharged patients with known identity.</p> <p>Conclusion</p> <p>More than half of the poisoned patients treated in pre-hospital treatment settings were discharged without transfer to higher levels. These poisonings were more often caused by drug and alcohol abuse than in those who were hospitalized, and more than two-thirds were males. Almost half of those discharged from ambulances received an antidote. The pre-hospital treatment of these poisonings appears safe regarding short-term mortality.</p

Database search engines : paradigms, challenges and solutions

The first step in identifying proteins from mass spectrometry based shotgun proteomics data is to infer peptides from tandem mass spectra, a task generally achieved using database search engines. In this chapter, the basic principles of database search engines are introduced with a focus on open source software, and the use of database search engines is demonstrated using the freely available SearchGUI interface. This chapter also discusses how to tackle general issues related to sequence database searching and shows how to minimize their impact