With the retirement of Sen. Ben Nelson (D) of Nebraska, announced Tuesday, Democrats have yet another open seat to defend in a 2012 election year that could flip control of the Senate to Republicans.

Democrats are defending 23 seats in the 2012 campaign cycle, compared with 10 for Republicans. With Democrats holding a 53-to-47 majority, Republicans need to pick up four seats to wrest control from them. If President Obama fails to win a second term, that threshold falls to three seats, because the vice president breaks tie votes.

“Given that the [Senate] majority is at stake, it’s a blow,” says Jennifer Duffy, senior editor of the Cook Political Report in Washington, of Senator Nelson's decision not to seek reelection next year.

“Nelson was going to face a very tough race, but you couldn’t write him off,” she adds. “He’s won difficult races before. There’s not an obvious candidate of his stature with the ability to raise money to replace him."

The two-term Nebraskan has been the Senate’s most reliable centrist, at a time when the ranks of moderates in Congress have been diminished almost to the point of extinction.

“Simply put: It is time to move on,” Nelson said in a video statement to Nebraskans on his Senate website. “I encourage those who will follow in my footsteps to look for common ground and to work together in bipartisan ways to do what’s best for the country, not just one political party.”

Often the lone Democrat voting with Republicans, Nelson broke party ranks to vote to extend the Bush-era tax cuts and to oppose legislation that gave some children of illegal immigrants a path to US citizenship. He joined with the so-called gang of 14 to work out a compromise over stalled judicial nominations, averting what was known at the time as the “nuclear option” to ban filibusters on judges. He’s also the lone Democrat in Nebraska’s congressional delegation.

Without Nelson’s support, Democrats could not have passed Mr. Obama’s health-care reform in 2010 – one of the president's campaign pledges. Nelson in the end gave Democrats the 60th vote they needed to block a GOP filibuster.

But that vote came at a cost. Senate majority leader Harry Reid kept the Senate in session for 25 days running, in a bid to overcome GOP stalling tactics. Senator Reid made many promises to wavering Democrats to bring them along, and he offered Nelson's home state special treatment to help pay for expanding Medicare coverage – a feature that came to be known as the “Cornhusker kickback.”

Under fierce criticism, Nelson often explained that he had not requested special treatment. At Nelson’s urging, the provision was dropped from the final version of the bill. But the criticism stuck and stung.

Nelson is still popular in Nebraska, where previously he had been a two-term governor. But he faced a tough reelection bid from a crowded Republican field that includes state Attorney General Jon Bruning, state Treasurer Don Stenberg, and state Sen. Deb Fischer. Former US Sen. Bob Kerrey (D), who recently stepped down as president of the New School in New York, is a prospect to run in Nelson's stead, but Mr. Kerrey has yet to express interest in the job. Most recently, Kerrey was in the running to head the Motion Picture Association of America.

Democratic Sens. Daniel Akaka of Hawaii, Jeff Bingaman of New Mexico, Kent Conrad of North Dakota, Herb Kohl of Wisconsin, Jim Webb of Virginia, and Independent Joseph Lieberman of Connecticut have also announced they will not run for reelection in 2012.